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The Rutgers Global Health Institute, part of Rutgers Biomedical and Health Sciences, Rutgers University, New Brunswick, New Jersey – A New Venture Designed to Improve Health and Wellness Globally  

Author: Gail S. Thornton, M.A.

Co-Editor: The VOICES of Patients, Hospital CEOs, HealthCare Providers, Caregivers and Families: Personal Experience with Critical Care and Invasive Medical Procedures

 

The newly formed Rutgers Global Health Institute, part of Rutgers Biomedical and Health Sciences (RBHS) of Rutgers University, New Brunswick, New Jersey (http://rbhs.rutgers.edu/), represents a new way of thinking by providing positive health outcomes to potential patients around the world affected by disease and/or by a negative environmental impact. The goal of the Institute is three-fold:

  • to improve the health and wellness of individuals and populations around the world,
  • to create a healthier world through innovation, engineering, and technology, and
  • to educate involved citizens and effective leaders in global health.

Richard G. Marlink, M.D., a former Harvard University professor recognized internationally for research and leadership in the fight against AIDS, was recently appointed as the inaugural Henry Rutgers Professor of Global Health and Director of the Rutgers Global Health Institute.

The Rutgers Global Health Institute was formed last year after research by the University into the most significant health issues affecting under-served and under-developed populations. While conducting research for its five-year strategic plan, the RBHS looked for bold and ambitious ways that they could take advantage of the changing health care environment and band together to tackle the world’s leading health and environmental causes, contributing to the betterment of society. One of the results was the formation of the Rutgers Global Health Institute, supporting cross-functionally Rutgers faculty, scientists, and clinicians who represent the best in their respective fields of health innovation, research and patient care related to global health.

More broadly, the RBHS, created in 2013, is one of the nation’s leading – and largest — academic health centers that provides health care education, research and clinical service and care. It is an umbrella organization that encompasses eight schools – Ernest Mario School of Pharmacy, Graduate School of Biomedical Sciences, New Jersey Medical School, Robert Wood Johnson Medical School, Rutgers School of Dental Medicine, School of Health Professions, School of Nursing and School of Public Health.

In addition, the RBHS encompasses six centers and institutes that provide cancer treatment and research, neuroscience, advanced biotechnology and medicine, environmental and occupational health and health care policy and aging research. Those centers and institutes are the Brain Health Institute, Center for Advanced Biotechnology and Medicine, Environmental and Occupational Health Sciences Institute, Institute for Health, Health Care Policy and Aging Research, Rutgers Cancer Institute of New Jersey, and Rutgers Institute for Translational Medicine and Research. And lastly, the RBHS includes the University Behavioral Health Care.

 

Rutgers Institute For Health Building

Image SOURCE: Photograph courtesy of the Rutgers Global Health Institute, Rutgers Biomedical and Health Sciences, Rutgers University, New Brunswick, New Jersey.   

 

Below is my interview with the Inaugural Henry Rutgers Professor of Global Health and Director of the Rutgers Global Health Institute Richard G. Marlink, M.D., which occurred in April, 2017.

You were recently appointed as the inaugural Henry Rutgers Professor of Global Health and Director of the new Rutgers Global Health Institute at Rutgers Biomedical and Health Sciences (RBHS). What are the goals of the new Institute?

Dr. Marlink: The overarching goal of the Rutgers Global Health Institute is to improve the health and wellness of individuals and populations in need both here and around the world, to create a healthier world through innovation, engineering, and technology, and to educate involved citizens and effective leaders in global health. We will do that by building on the aspiration of our originating organization — RBHS, which is to be recognized as one of the best academic health centers in the U.S., known for its education, research, clinical care, and commitment to improving access to health care and reducing health care disparities.

As the newly formed Rutgers Global Health Institute, we are embarking on an ambitious agenda to take advantage of the changing health care environment. Working across schools and disciplines at Rutgers University, we plan to have a significant impact within at least four signature programs identified by RBHS, which are cancer, environmental and occupational health, infection and inflammation, and public health. We also will include all other parts of Rutgers, as desired, beyond RBHS.

My background as a global health researcher, physician, and leader of grassroots health care delivery will help develop programs to undertake global health initiatives that assist populations locally and around the world. I believe that involved citizens, including students, can greatly impact major societal issues.

A key role in the strategic growth of Rutgers Biomedical and Health Sciences – an umbrella organization for eight schools, four centers and institutes and a behavioral health network — is to broaden the Rutgers University’s presence in the public health community globally to improve health and wellness. How will the new Rutgers Global Health Institute be part of this growth?

Dr. Marlink: Our RBHS Chancellor Brian Strom [M.D., M.P.H.] believes that we are positioned to become one of the finest research universities in the country, working cross-functionally with our three campuses in Newark, Camden and New Brunswick. In developing the strategic plan, Dr. Strom notes that we become much stronger and more capable and productive by leveraging our strengths to collaborate and working together across disciplines to best serve the needs of our community locally and globally.

Specifically, we are formulating plans to focus on these areas: old and new infectious disease epidemics; the expanding burden of noncommunicable diseases in poor populations; the social and environmental threats to health, poverty and humanitarian crises; and inadequate local and developing country health systems. We will support the development of global health research programs university-wide, the recruitment of faculty with interests in global health, and the creation of a web-based global health resource center for faculty and students with interests in these areas.

We are still a very young part of RBHS, and of Rutgers overall, so our plans are a work in progress. As tangible examples of our commitment to improving health and wellness globally, we plan to enhance global public health by establishing links between global public health and environmental and occupational health faculty in studies related to air pollution, climate change, and pesticide health.

Another example the Institute has in the works is expanding links with the School of Engineering. In fact, we are creating a senior-level joint faculty position with the School of Engineering and Rutgers-New Brunswick. Still other plans involve forging collaborative relationships between the Rutgers Cancer Program, under the auspices of Rutgers Cancer Institute of New Jersey, which is New Jersey’s only National Cancer Institute (NCI)-designated comprehensive cancer center, and other organizations and partners around the world, especially in poor and less-developed countries.

How is the Rutgers Global Health Institute strategically prepared for changing the health care paradigm?

Dr. Marlink: We intend to be an international global health leader in the health sciences, in public health, and in other related, but non-biomedical professions. This means that we will incorporate our learnings from laboratory sciences and the clinical, behavioral, and public health sciences, as well as from engineering, business, economics, law, and social sciences. This broad approach is critical in this health care environment as accountability for patient care is shifting to large groups of providers. Health care will be more value-driven and our health care teams must work collaboratively to be innovative. Our focus on health care is now also population-based, rather than only individual-based, and we are moving from large regional centers toward community centers, even in small and remote areas of the world. We are encouraged by rapid changes in technology that will provide new opportunities for shared knowledge, patient care and research.

Additionally, we are exploring ways to identify and recruit key faculty who will increase our breadth and depth of key disease areas as well as provide guidance on how to pursue science grants from the National Institute of Health (NIH)-funded program project grants and specialized research programs.

Currently, Rutgers University receives NIH funding for research in public health, population health, health promotion, wellness, health behavior, preventive medicine, and global health.

As a researcher, scholar and leader of grassroots health care delivery, how have your past positions prepared you for this new challenge? Your last position was the Bruce A. Beal, Robert L. Beal, and Alexander S. Beal Professor of the Practice of Public Health at Harvard University’s T.H. Chan School of Public Health and Executive Director of the Harvard AIDS Initiative.

Dr. Marlink: I have been a global health practitioner, researcher, and executive leader for almost three decades. I am trained in medical oncology and HIV medicine and have conducted clinical, epidemiological and implementation research in Africa since 1985. I was first introduced to global health when finishing my Hematology/Oncology fellowship at what is now the Beth Israel Deaconess Medical Center in the mid-1980’s in Boston.

During my Hematology/Oncology fellowship and after the co-organizing the first, hospital-based AIDS care clinic in the New England region, I was trying to learn the ropes in virology and molecular biology in the laboratory group of Max Essex at Harvard University. During that time in the mid-1980s, our laboratory group along with Senegalese and French collaborators discovered the first evidence for the existence of a new human retrovirus, HIV-2, a distinct second type of human AIDS virus, with its apparent origins in West Africa.

As a clinician, I was able to assist in Senegal, helping set up clinical care and create a research cohort in Dakar for hundreds of women sex workers infected with this new human retrovirus and care for them and their families. I discovered that a little can go a long way in poor settings, such as in Senegal. I became hooked on helping create solutions to help people in poor settings in Africa and elsewhere. Long-term partnerships and friendships have subsequently been made in many developing countries. Throughout my career, I have built successful partnerships with many governments, companies, and non-profit organizations, and those relationships have been the foundation to build successful public health partnerships in poor regions of the world.

In the 1990s, I helped create the Botswana-Harvard Partnership for HIV Research and Education (BHP). Through this partnership, the Government of Botswana and BHP have worked together to combat the AIDS epidemic in Botswana. Under my direction, and in partnership with the Botswana Ministry of Health, BHP launched the KITSO AIDS Training Program in 1999. Kitso is the Setswana word for ‘knowledge.”

KITSO is the national training program for physicians, nurses, and pharmacists, which has trained more than 14,000 health professionals in HIV/AIDS care and antiretroviral treatment. KITSO training modules address issues, such as antiretroviral therapy, HIV/AIDS-related disease management, gender-specific HIV issues, task-sharing, supportive and palliative care, and various psychosocial and counseling themes.

In addition, I was the Botswana County Director for Harvard Chan School’s 3-country President’s Emergency Plan AIDS Relief (PEPFAR) grant, The Botswana PEPFAR effort includes a Clinical and Laboratory Master Training Program and the creation of the Botswana Ministry of Health’s Monitoring and Evaluation Unit. Concurrently, I was the Principal Investigator of Project HEART in five African countries with the Elizabeth Glaser Pediatric AIDS Foundation.

Also in Botswana, in 2000, I was a co-founder of a distinct partnership involving a large commitment to the Government of Botswana from the Bill and Melinda Gates and Merck Foundations.  This commitment continues as an independent non-governmental organization (NGO) to provide support for various AIDS prevention and care efforts in Botswana and the region.

All these global health experiences, it seems, have led me to my new role at the Rutgers Global Health Institute.

What is your advice for ways that the business community or university students can positively impact major societal issues?

Dr. Marlink: My advice is to be optimistic and follow that desire to want to make a difference. Margaret Mead, the American cultural anthropologist, said years ago, “Never doubt that a small group of thoughtful, committed citizens can change the world; indeed, it’s the only thing that ever has.” I believe that to be our guiding principle as we embark on this new initiative.

I also believe that students should become specialized in specific areas prior to going fully into “global health,” as they develop in their careers, since they will then add more value later. For example, students should be grounded in the theory of global health in their undergraduate studies and then develop a specialization, such as becoming a statistician, economist, or medical doctor, to make a longer and greater impact in improving global health. As for the business community, we are looking for committed individuals who are specialized in specific areas to bring their knowledge to our organization, as partners in the fight against disease, improving the environment, or helping with humanitarian issues. We are committed to improving health and wellness, increasing access to the best health care, and reducing health disparities.

What is it about your current role that you enjoy the most?

Dr. Marlink: I enjoy building research, learning, and clinical programs, as I have in the HIV arena since the early 1980s. At that time, there were limited resources and funding, but a willingness among universities, non-governmental organizations, hospitals and the pharmaceutical industry to make a difference. Today in my new role, I’d like all of us to have an impact on health and wellness for those in need – to build programs from the ground up while partnering with organizations with the same goal in mind. I know it can be done.

Over my career, when I have a patient here or in a developed country who has been diagnosed with cancer, but is cured or in remission, that puts a huge smile on my face and in my heart. It also impacts you for the rest of your life. Or when I see an infant born without HIV because of the local country programs that are put in place, that also makes me feel so fulfilled, so happy.

I have worked with many talented individuals who have become great friends and partners over my career who have helped create a positive life for under-served populations around the world. We need to remember that progress happens with one person at a time or one program at a time. That’s how you truly improve health around the world.

 

Headshot - 2016

Image SOURCE: Photograph of Inaugural Henry Rutgers Professor of Global Health and Director of the Rutgers Global Health Institute at Rutgers Biomedical and Health Sciences, courtesy of Rutgers University, New Brunswick, New Jersey.

Richard G. Marlink, M.D.
Inaugural Henry Rutgers Professor of Global Health

Director of the Rutgers Global Health Institute

Rutgers Biomedical and Health Sciences

Richard G. Marlink, M.D., a Harvard University professor recognized internationally for research and leadership in the fight against AIDS, was recently appointed as the inaugural Henry Rutgers Professor of Global Health and Director of a new Rutgers Global Health Institute at Rutgers Biomedical and Health Sciences (RBHS). His role is to develop the strategic growth of RBHS by broadening the Rutgers University’s presence in the public health community to improve health and wellness.

Previously, Dr. Marlink was the Bruce A. Beal, Robert L. Beal, and Alexander S. Beal Professor of the Practice of Public Health at Harvard’s T.H. Chan School of Public Health and Executive Director of the Harvard AIDS Initiative.

At the start of the AIDS epidemic, Dr. Marlink was instrumental in setting up the first, hospital-based HIV/AIDS clinic in Boston, Massachusetts, and studied the impact of the HIV virus in west and central Africa. After helping to start the Botswana-Harvard Partnership in 1996, he founded the Kitso AIDS Training Program, which would become Botswana’s national AIDS training program. Kitso means knowledge in the local Setswana language.

Dr. Marlink was the principal investigator for the Tshepo Study, the first large-scale antiretroviral treatment study in Botswana, in addition to conducting other clinical and epidemiological studies in the region. Also in Botswana, he was the country director for Harvard’s contribution to the joint Botswana and United States governments’ HIV/AIDS and TB training, monitoring and evaluation PEPFAR effort.

In the mid-1980s in Senegal, Dr. Marlink was part of the team of Senegalese, French and American researchers who discovered and then studied the second type of human AIDS virus, HIV-2. Since then, he has been involved in multiple HIV/AIDS care, treatment and prevention programs in many African countries, including in Botswana, Côte d’Ivoire (Ivory Coast), Democratic Republic of the Congo, Kenya, Lesotho, Malawi, Mozambique, Rwanda, Senegal, South Africa, Swaziland, Tanzania, Uganda, Zambia and Zimbabwe. He has also organized initiatives to enhance HIV/AIDS care in Brazil, Puerto Rico and Thailand.

Dr. Marlink has served as the scientific director, the vice president for implementation and the senior adviser for medical and scientific affairs at the Elizabeth Glaser Pediatric AIDS Foundation, where he was principal investigator of Project HEART, a five-country CDC/PEPFAR effort in Africa. That project began in 2004 and by 2011 had placed more than 1 million people living with HIV into care clinics. More than 565,000 of these people were placed on life-saving antiretroviral treatment.

Since 2000, Dr. Marlink has been the founding member of the board of directors of the African Comprehensive HIV/AIDS Partnerships, a public-partnership among the government of Botswana and the Bill and Melinda Gates and Merck Foundations to provide ongoing support for numerous HIV/AIDS prevention, care and treatment efforts in that country.

He has authored or co-authored more than 130 scientific articles; written a textbook, Global AIDS Crisis: A Reference Handbook; and co-edited the book, AIDS in Africa, 2nd Edition. Additionally, he served as chief editor for two special supplements to the journal AIDS and as executive editor of the seminal 320-author, three-volume textbook, From the Ground Up: A Guide to Building Comprehensive HIV/AIDS Care Programs in Resource Limited Settings.

A trained fellow in hematology/oncology at the Beth Israel Deaconess Medical Center at Harvard Medical School, Dr. Marlink received his medical degree from the University of New Mexico and his bachelor’s degree from Brown University.

 

Editor’s note:

We would like to thank Marilyn DiGiaccobe, head of Partnerships and Strategic Initiatives, at the Rutgers Global Health Institute, for the help and support she provided during this interview.

 

REFERENCE/SOURCE

Rutgers Biomedical and Health Sciences (http://rbhs.rutgers.edu/)

Other related articles

Retrieved from https://aids.harvard.edu/ 

Retrieved from http://b.3cdn.net/glaser/515eaa8068b5e71d44_mlbrof7xw.pdf 

Other related articles were published in this Open Access Online Scientific Journal include the following: 

2016

CRISPR/Cas9 and HIV1 

https://pharmaceuticalintelligence.com/2016/04/16/crisprcas9-and-hiv1/

Concerns About Viruses

https://pharmaceuticalintelligence.com/2016/01/29/concerns-about-viruses/

CD-4 Therapy for Solid Tumors

https://pharmaceuticalintelligence.com/2016/05/02/cd-4-therapy-for-solid-tumors/

Novel Discoveries in Molecular Biology and Biomedical Science

https://pharmaceuticalintelligence.com/2016/05/30/novel-discoveries-in-molecular-biology-and-biomedical-science/

Scientists eliminate HIV1 DNA from the genome and prevent reinfection

https://pharmaceuticalintelligence.com/2016/03/23/scientists-eliminate-hiv1-dna-from-the-genome-and-prevent-reinfection/

Double Downside of HIV CRISPR therapy

https://pharmaceuticalintelligence.com/2016/04/09/double-downside-of-hiv-crispr-therapy/

2015

Where Infection meets with Cancer: Kaposi’s sarcoma (KS) is the most common cancer in HIV-1-infected persons and is caused by one of only 7 human cancer viruses, i.e., human herpesvirus 8 (HHV-8)

https://pharmaceuticalintelligence.com/2015/10/20/where-infection-meets-with-cancer-kaposis-sarcoma-ks-is-the-most-common-cancer-in-hiv-1-infected-persons-and-is-caused-by-one-of-only-7-human-cancer-viruses-i-e-human-herpesvirus-8-hhv/

Antibody shows promise as treatment for HIV

https://pharmaceuticalintelligence.com/2015/04/09/antibody-shows-promise-as-treatment-for-hiv/

2014

AIDS: Origin of HIV pandemic ‘was 1920s Kinshasa’

https://pharmaceuticalintelligence.com/2014/10/10/aids-origin-of-hiv-pandemic-was-1920s-kinshasa/

2013

Scientists discover how AIDS virus enters key immune cells

https://pharmaceuticalintelligence.com/2013/12/31/scientists-discover-how-aids-virus-enters-key-immune-cells/

Heroes in Medical Research: Dr. Robert Ting, Ph.D. and Retrovirus in AIDS and Cancer

https://pharmaceuticalintelligence.com/2013/04/17/heroes-in-medical-research-dr-robert-ting-ph-d-and-retrovirus-in-aids-and-cancer/

2012

Nanotechnology and HIV/AIDS treatment

https://pharmaceuticalintelligence.com/2012/12/25/nanotechnology-and-hivaids-treatment/

HIV vaccine: Caltech puts us One step further

https://pharmaceuticalintelligence.com/2012/08/31/hiv-vaccine-caltech-puts-us-one-step-further/

Bone Marrow Transplant Eliminates Signs of HIV Infection

https://pharmaceuticalintelligence.com/2012/07/29/bone-marrow-transplant-eliminates-signs-of-hiv-infection/

Getting Better: Documentary Videos on Medical Progress — in Surgery, Leukemia, and HIV/AIDS

https://pharmaceuticalintelligence.com/2012/08/23/getting-better-documentary-videos-on-medical-progress-in-surgery-leukemia-and-hivaids/

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Swiss Paraplegic Centre, Nottwil, Switzerland – A World-Class Clinic for Spinal Cord Injuries

Author: Gail S. Thornton, M.A.

Co-Editor: The VOICES of Patients, Hospital CEOs, HealthCare Providers, Caregivers and Families: Personal Experience with Critical Care and Invasive Medical Procedures

 

The Swiss Paraplegic Centre (SPC, www.paraplegie.ch) in Nottwil, Switzerland, is a privately owned, leading acute care and specialist hospital employing more than 1,500 health professionals in 80 different occupations that focuses on world-class primary care and comprehensive rehabilitation of patients with spinal cord injuries. In addition to the SPC’s extensive range of medical and therapeutic care, treatment and services, the hospital offers advisory services, as well as research in the areas of paraplegia [paralysis of the legs and lower body, typically caused by spinal injury or disease], tetraplegia [also known as quadriplegia, paralysis caused by illness or injury that results in the partial or total loss of use of all four limbs and torso], prevention and related conditions. With 150 beds, the SPC provides modern facilities for rehabilitation and therapy, diagnostics, surgery, ongoing care, orthopedic technology, as well as social services and 24-hour emergency care.

In its 26-year history, the SPC has provided treatment and care to more than 20,000 in-patients. That number continues to grow exponentially due to the reputation of the SPC. In fact, the SPC’s staff performs their duties with effectiveness, expediency and cost-efficiency measures, requiring highly developed process-led medicine, centered around the needs of the patient.

The areas of medical specialty and centers of excellence include the Swiss Paraplegic Centre (SPC), the Swiss Spinal Column and Spinal Cord Centre (SWRZ), the Centre for Pain Medicine (ZSM) and the Swiss Olympic Medical Center (SOMC). These centers respectively offer patients cutting-edge medical treatment based on the most advanced research in areas covering treatment and rehabilitation cases of acute paraplegia, vertebral and spinal cord surgery, as well as services relating to pain management, sports medicine and preventive health checks.

Alongside the core focus on paraplegiology, the SPC is also equipped with the necessary medical facilities, allowing for the lifelong care of paraplegic patients. The SPC provides individually-tailored, comprehensive treatment in three phases (acute, reactivation and integration) using highly skilled staff and state-of-the-art equipment. The aim is always to re-establish a patient’s personal functionality, self-image and lifestyle to the fullest possible extent, with a holistic approach to treatment that includes mental, physical and psycho-social aspects, such as career, family and leisure activities.

Specialist services available at the SPC include amongst others orthopedics, neuro-urology, pain medicine, sports medicine, prevention, clinical research, emergency medicine, vehicle conversion and rehabilitation techniques. Medico-therapeutic treatments, such as physiotherapy, ergotherapy and training therapy are available, alongside advice and counseling services, such as professional reintegration.

The SPC is the largest of Switzerland’s four special hospitals for paraplegics and tetraplegics located in Nottwil/Lucerne, a town in central Switzerland on the shores of Lake Sempach. The other three facilities are in Basel, Sion and Zurich. Nowadays, the SPC consistently treats more than 60 percent of people with spinal cord injury in Switzerland and is fully occupied year-round. 

Image SOURCE: Photographs courtesy of Swiss Paraplegic Centre, Nottwil, Switzerland.  Interior and exterior photographs of the hospital.

 

Below is my interview with Hospital Director Dr. Med. Hans Peter Gmünder, M.D., which occurred in March, 2017.

 As a privately owned clinic with a specialty in the rehabilitation of patients with spinal cord injuries, how do you keep the spirit of research and innovation alive?

Dr. Med. (medicinae) Gmünder: The goal of the Swiss Paraplegic Foundation, an umbrella organization that encompasses the Swiss Paraplegic Centre, is to create a unique network of services for people with spinal cord injury, from primary care through to the end of their lives. Its aim is to provide comprehensive rehabilitation and to reintegrate those affected into family life, society and the working environment.

We want to maintain our pioneering and leading role in the fields of acute medicine, rehabilitation and lifelong assistance to people with spinal cord injuries. By providing a comprehensive network of services featuring solidarity, medical care, integration and lifelong assistance, as well as research all in one place, we are unique in Switzerland and in other countries around the world.

People with spinal cord injury rely upon our network of services, which are at their disposal throughout their lives. The challenge facing us is to continually adapt these services to reflect current research and treatment to comply with our mission of delivering high-quality services. The trust which has been placed in us obliges us to continue our success story.

We have our own research department, closely linked to the Swiss Paraplegic Centre, and dedicated employees who draw upon their wide-ranging professional networks to stay on top of the latest international research.

We have a few examples that we’d like to share with you.

  • In 2013, the World Health Organization (WHO) published its first international health report on the topic of spinal cord injury, “International Perspectives on Spinal Cord Injury.” It was developed in collaboration with Swiss Paraplegic Research in Nottwil and a team of international experts.
  • In the summer of 2014, the Swiss Paraplegic Centre became the first rehabilitation center in Switzerland to implement exoskeletons [external covering for the body that provides both support and protection] in the rehabilitation and training of patients with spinal cord injury. Our experiences are included in an international study, and will contribute to the development of useful mobility aids for people with spinal cord injuries.

At the end of October 2016, an estimated 9,000 visitors came to Nottwil for two days of celebrations to mark five anniversaries — the Swiss Paraplegic Foundation turned 40, the Swiss Paraplegics Association was 35, the Swiss Paraplegic Centre celebrated 25 years, Swiss Paraplegic Research reached 15 years, and it was the 80th birthday of the founder and honorary president, Dr. Med. Guido A. Zäch, M.D.

What draws patients to the Swiss Paraplegic Centre?

Dr. Gmünder: We support people with spinal cord injuries throughout their lives. It is the unique, holistic approach to acute medicine, rehabilitation and lifelong medical, professional and social assistance that draws patients from Switzerland and many other countries to our clinic in Nottwil.

For example, in cases where we have individuals involved in serious accidents, the comprehensive rehabilitation of a patient with spinal cord injury begins at the scene of the accident. The aim of comprehensive assistance follows in three stages – acute, reactivation and integration phase – through the appropriate, individual deployment of specialist personnel and instruments. We rescue the individual at the scene of the accident and provide the right acute therapy. What follows is an initial rehabilitation through specialists in diagnosis, surgery, therapy and care, and then comes lifelong support and care with the aid of specialists.

Following the disproportionately high percentage of people with tetraplegia admitted to the Centre for initial rehabilitation in 2014, our specialist clinic reported a higher proportion of people with paraplegia in 2015. Spinal cord injuries resulted from an accident in around half of all initial rehabilitation cases: falls led to the spinal cord injury in the case of 43 percent of people affected, sports accidents with 35 percent and road traffic accidents in 18 percent. In fact, 52,482 nursing days were clocked for a total of 1,085 in-patients who were discharged from the clinic after initial rehabilitation or follow-up treatment in 2015.

In fact, some of our patient success stories mentioned on our web site involve these individuals:

“I was a cheesemaker for 33 years with my own dairy; gardening was my second love. That was before I had my accident helping out on my son’s farm. I need a new hobby now that I will enjoy, that will fill my time and give me something to do when I get back home. Making art out of lime wood could appeal to me. While it is difficult for me to make the small cuts in the wood as I lack strength in my hand, patience will reap rewards. My most important objective? To be able to stand on my own feet and take a few steps again. I should have achieved that by the time I am discharged from the clinic in five months.” — Josef Kobler (58), tetraplegic following an accident.

“Since being diagnosed with a spinal cord injury, I come back to Nottwil a lot. For instance, to go the Wheelchair Mechanics Department to have the settings of my new wheelchair optimized. It replaces my legs and must fit my body perfectly. However, in most cases I attend the Centre for Pain Medicine of the SPC as an outpatient in order to have the extremely severe pains and muscle cramps, which I suffer from every day, alleviated. They became so severe that I had a pain pump with medication implanted at the SPC. It is apparent now that unfortunately the effect isn’t permanent. We are now giving electrostimulation a try. This involves applying electrodes to the vertebral canal. If I could finally get my pain under control, I would be able to return to work and set up my own business. That is my biggest wish. I have had an idea about what I could do.” — Hervé Brohon (41), paraplegic following an accident.

“I have always been passionate about cooking and have enjoyed treating my family and guests to my dishes and to the aperitifs that I have created myself. I absolutely want to be able to do that again. As independently as possible, of course. That is my objective. I have availed of the opportunity on a few occasions to try out the obstacle-free practice apartment and kitchen at the SPC. If I am able to go home in four weeks, my kitchen will also be adapted to be wheelchair-friendly. Whether I am cooking for two, four or six people is a much bigger consideration as a wheelchair user. I now have to consciously allow for time and effort. However, one thing is certain: I can’t wait to welcome my first guests.” — Isa Bapst (73), paraplegic following an accident.

How is the Swiss Paraplegic Centre transforming health care?

Dr. Gmünder: The Swiss Paraplegic Centre offers an integrated healthcare structure, including a wide range of medical specialists covering every aspect of medical care for those with spinal cord injuries.

In selected core disciplines for the care of people with spinal cord injuries, we also treat a large number of patients without spinal cord injuries. This relates primarily to pain medicine, spine- and spinal cord surgery and respiratory medicine.

In fact, the Swiss Paraplegic Foundation, our umbrella organization, has been an unbelievable success story, operating a network of services to benefit people with spinal cord injury.

Our Chairman of the Board of Trustees, Dr. Sc. Techn. (scientiae technicarum) Daniel Joggi, knows what it’s like to become totally dependent as he has been in a wheelchair for the past four decades.

Dr. Joggi tells his story: “I have been a wheelchair user ever since I had a skiing accident 39 years ago. I know what it is like to become totally dependent from one second to the next. How doggedly you have to battle to recover as much of your mobility as possible and, more especially, to be able to live a self-determined life again after a long process of resilience. The inner resolve it takes to plot a new course in life, to have relationships with others from a different perspective and to acquire new job skills. Therefore, I am eternally grateful along with all the other people in Switzerland with paraplegia and tetraplegia for the help, support and great solidarity that allow the Foundation to deliver all the services which are so immensely valuable to us.”

At the Swiss Paraplegic Centre, a 24-hour emergency department is staffed to handle any emergency. Please provide your thoughts on this critical component of diagnosis and care for newly diagnosed patients.

Dr. Gmünder: Yes, our Centre is recognized by the Swiss Union of Surgical Societies as a specialist clinic for first-aid treatment of paraplegics.

Statistics and experience clearly show that in 80 out of 100 cases, the damage to the spine and the spinal cord is not definite immediately after an accident. In the first six hours, there are real chances to mitigate or even avoid an imminent cross-paralysis. After that it is usually too late.

In addition to transferring an individual directly to the SPC, appropriate acute care is another important criterion for the success of the individual affected by spinal cord issues. That means that individuals are in the right place for the subsequent, comprehensive rehabilitation.

The benefits for our patients are:

  • Emergency service around the clock by specialists trained to minimize damage to the spinal cord and spine;
  • Admission and treatment of all patients with paraplegia from all over Switzerland;
  • Specific knowledge and practical experience in comprehensive rehabilitation of paraplegics;
  • Comprehensive range of medical and therapeutic services under one roof;
  • Modern equipment for precise, careful diagnostics and operations;
  • Consultancy and network for external experts in areas not covered by the SPC;
  • Interdisciplinary work in well-established teams; and
  • Central location proximity and quick access from all parts of the country.

What is your connection to the Swiss Paraplegic Research and its mission of getting “strategy into research” and “research into practice?”

Dr. Gmünder: The Swiss Paraplegic Research (SPR), connected to the Swiss Paraplegic Centre, is part of the Swiss Paraplegic Foundation (SPF) and is an integral part of the Nottwil campus.

It is the mission of Swiss Paraplegic Research to sustainably improve the situation of people with paraplegia or tetraplegia through clinical and interdisciplinary research in the long-term. The areas that are aimed to be improved are functioning, social integration, equality of opportunity, health, self-determination and quality of life.

Our Swiss Paraplegic Research has been supported by the Federal Government of Switzerland and by the Canton of Lucerne for eight years as a non-university research institution. We are proud of this accomplishment.

Our main research domains are in the areas of aging, neuro-rehabilitation, musculo-skeletal health, preserving and improving function of upper limbs, pain, pressure sores, respiration, urology and orthopedics.

The goal of Swiss Paraplegic Research is to promote the study of health from a holistic point of view, by focusing on the ‘lived experience’ of persons with health conditions and their interaction with society. We are, therefore, establishing a research network for rehabilitation research from a comprehensive perspective on a national and international level. This network will make it possible to practically apply the latest research findings to provide the best possible care and reintegration for people with paraplegia or tetraplegia.

This year, we received the approval of 18 new research projects and we had a total of 36 studies in progress under review, undertaken by and with the involvement of the Clinical Trial Unit (CTU), the department for clinical research at the Centre. For example, the successful implementation of a multi-center study on the use of walking robots (exoskeleton) merits special mention. Research was carried out in that study into the wide range of effects of maintaining movement for people with spinal cord injury.

The CTU will continue to carry out research in Rehabilitation Engineering in a cooperation with Burgdorf University of Applied Science and the research group headed by Professor Kenneth Hunt. The “Life and Care” symposium on breathing and respiration organized by the CTU provided a platform for an international knowledge exchange with national and international experts. This is crucial for further scientific development in respiratory medicine. In 2015, the CTU also launched the CTU Central Switzerland, in association with Lucerne Cantonal Hospital and the University of Lucerne. It supports clinics which are actively engaged in research with specific services, thereby enhancing Switzerland’s standing as a center of research.

How does the Swiss Paraplegic Foundation support your vision?

Dr. Gmünder: The Swiss Paraplegic Group includes the Swiss Paraplegic Foundation, which was established in 1975, two partner organizations — the Benefactors’ Association and the Swiss Paraplegics Association, and six companies owned by the Foundation. Those six companies are the Swiss Paraplegic Centre, the Swiss Paraplegic Research, Orthotec AG, ParaHelp AG, Sirmed Swiss Institute of Emergency Medicine AG, Seminarhotel Sempachersee AG.

The Swiss Paraplegic Foundation, founded by Dr. Med. Guido A. Zäch in 1975, is a solidarity network for people with spinal cord injuries, unrivaled anywhere in the world. Its work is based on the vision of medical care and comprehensive rehabilitation for people with paraplegia and tetraplegia, with a view towards enabling them to lead their lives with self-determination and with as much independence as possible, supported by the latest advances in science and technology.

The unique network of services of the Foundation is a strategic mix of Solidarity, Research, Medicine and Integration and Lifelong Assistance. Let me elaborate on these services.

  • Solidarity
    • The Foundation provides a comprehensive range of services for every area of a person’s life who has a spinal cord injury. The Nottwil campus serves to be a center of excellence for integration, assistance and lifelong learning for our patients.
    • The Foundation ensures that its benefactors and donors are aware of our list of services and can support us longer term.
    • The Foundation establishes a national and international network that will guarantee better basic conditions for people with spinal cord injury.
    • The Foundation encourages training of specialized personnel in the field of spinal cord injury.
  • Research
    • The Foundation contributes to the sustainable improvement of health, social integration, equal opportunities and self-determination of people with spinal cord injury by carrying out rehabilitation research.
    • The Foundation works closely with the World Health Organization (WHO) and encourages exchanges with universities and institutions locally and globally for the latest scientific findings and conducts academic training at the University of Lucerne.
    • The Foundation develops high-quality care standards for its patients.
  • Medicine
    • The Foundation offers all medical services needed for professional acute care and rehabilitation of people with spinal cord injury and encourages patients to become involved in their therapy and to take responsibility for their lives.
    • The Foundation strengthens relationships with partners in specific disciplines and local institutions to benefit people with spinal cord injury.
    • The Foundation is a member of committees with political influence to ensure that its patients receive highly specialized medical care.
  • Integration and Lifelong Assistance
    • The Foundation establishes a network throughout Switzerland to help people with spinal cord injury.
    • The Foundation offers comprehensive services to meet people’s needs to improve their integration into society.
    • The Foundation encourages people with spinal cord injury to lead an independent life and educate family and friends so they can provide the necessary support.

Moreover, in cases of hardship, the Foundation makes contributions towards the cost of walking aids, equipment and amenities for people with paraplegia and tetraplegia. It also takes on uncovered hospital and care costs.

 Current market research shows that the Swiss Paraplegic Foundation ranks among the three most highly rated aid organizations in Switzerland. Can you please elaborate on why?

Dr. Gmünder: That is true. The Foundation is highly rated in terms of goodwill, innovation, competence and effectiveness. In addition, it is regarded as undoubtedly the most competent organization representing people with disabilities in Switzerland, according to several market research surveys.

So that we can continue to meet the demand for our patients, families and other visitors, plans are under way to upgrade our clinic and hotel on our premises.

We generally have interest from visitors to visit our Centre. Our guided tours and events enabled the general public to see how the foundation concept is put into practice, day in, day out. In Nottwil, 160 guides provided more than 11,000 visitors with a glimpse into the operations at our specialist clinic.

Additionally, we organized more than 5,000 scientific meetings attended by more than 170,000 people in 2015. And our wheelchair athletes take part in two major competitions, the IPC Athletics Grand Prix and the UCI Para-cycling World Championships, at our Nottwil site. It is our hope to continue to motivate individuals with spinal cord injuries to be involved in healthy exercise.

Since you became Hospital Director, how have you changed the way that you deliver health care or interact with patients?

Dr. Gmünder: It is important to me that the patients and their needs are the focus of our efforts. As such, one of my main tasks is to align our processes with our patients.

Here are some examples:

We started construction with a newly expanded Intensive Care Medicine, Pain Medicine and Surgical Medicine department last year to provide patients with an expanded variety of cross-linked treatments.

Certified as a nationwide trauma center, our Swiss Spinal Column and Spinal Cord Centre has become increasingly recognized throughout the country with large numbers of non-paralyzed patients, who have severe spinal cord injury, being referred to our facility. It is under the medical leadership of the Head of Department Dr. Med. Martin Baur, M.D. This highly specialized acute care facility recently received certification as a specialist center for traumatology within the Central Swiss Trauma Network.

We believe in developing the next generation of professionals and our Department of Anesthesia was recognized as a center of further training; the first two junior doctors have been appointed and postgraduate courses in anesthesia nursing are already available.

Our Swiss Weaning Centre, where individuals learn to breathe without a machine, has brought specialists from Intensive Care Medicine, Speech Therapy, RespiCare and Spinal Cord Medicine even closer together in a new process structure for respiratory medicine. At the same time, the Swiss Weaning Centre reported increased referrals from university hospitals and private clinics, as well as numerous successes with patients who had proved to be difficult to wean from respiratory equipment.

Our Centre for Pain Medicine, one of the largest pain facilities in the country, reported a further increase in inpatient treatments. Epiduroscopy, which was introduced in 2014, has proved to be a success. It is a percutaneous, minimally invasive procedure which is used in the diagnosis and treatment of pain syndromes near the spinal cord.

We reached a milestone in tetra hand surgery. The team of our doctors has been consulting at two other spinal cord injury centers and have used these occasions to show doctors around the country what possibilities there are for improved hand and grip functions, leading to an enhanced quality of life.

In what ways do you rehabilitate the whole patient? Why is this important early on in treatment?

Dr. Gmünder: In accordance with our vision, we are not just focusing on physical rehabilitation but on the entire person in their social environment (leisure, work, housing, mobility). Due to our broad organizational structure, we have many resources at our disposal. The rate of reintegration for people who did their primary rehabilitation at the Swiss Paraplegic Centre is almost 65 percent – one of the highest in the world.

Because we work to address diagnosis, treatment and management of traumatic spinal cord injuries with our patients, we take great care in working with patients on their medical disabilities, physical disabilities, psychological disabilities, vocational disabilities, social aspects and any health complications. That means that we not only treat patient’s medically, but also we treat them through therapy and complementary medicine, such as art therapy, sports and water therapy and homeopathic medicine.

At the SPC, we nurture a culture which is characterized by common values and shared objectives, namely commitment, leadership, a humane approach, cooperation and openness and fairness in our dealing with one another and with our patients.

As you follow patients throughout their rehabilitation and treatment, what are you most proud of at the Centre? 

Dr. Gmünder: Research has shown that early referral of a patient with a traumatic spinal injury lessens the complications, shortens the length of time in the hospital and is, therefore, more cost-effective.

We are confronted by individuals every day whose abilities have been limited by disease, trauma, congenital disorders or pain – and we are focused on enabling them to achieve their maximum functional abilities. Our patients have a better outcome and quality of life, patient-focused treatment, ongoing case management, and lifelong care.

It’s important to emphasize that our comprehensive rehabilitation of individuals with spinal cord injuries begins on the first day after the accident or trauma. On one hand, the medical treatments with paraplegia or tetraplegia are performed by a multidisciplinary medical team. And on the other hand, it is our goal to give those individuals their personality and life structure as quickly – and as best – as possible. An individual’s medical condition affects their psychological, physical and social aspects of life.

We focus on individualized treatment for the greatest possible independence for our patients. When patients are satisfied with our work and its results, they can resume a self-determined life. That is our greatest joy.

Hans Peter Gmuender

Image SOURCE: Photograph of Hospital Director Hans Peter Gmünder, M.D., courtesy of Swiss Paraplegic Centre, Nottwil, Switzerland.

Hans Peter Gmünder, M.D.
Hospital Director

Hans Peter Gmünder, M.D., assumed the role of Hospital Director of the Swiss Paraplegic Centre in 2011.  He is a German-Belgian double citizen.

Previously, Dr. Gmünder was Chief Physician and Medical Director of the Rehaklinik Bellikon, a rehabilitation and specialist clinic for traumatic acute rehabilitation, sports medicine, professional integration and medical expertise for 10 years in the canton of Aargau, Switzerland. He began his career at the Swiss Paraplegic Centre in the 1990s as Assistant and Senior Physician, and later as Chief Physician and Deputy Chief Physician.

He completed a B.S. degree in Business Administration at SRH FernHochschule Riedlingen in 2010 and an M.D. degree at Freie Universität Berlin in 1987.

He is married to Sabeth and is the father of two children.

 

Editor’s note:

We would like to thank Claudia Merkel, head of public relations, Swiss Paraplegic Centre,  for the help and support she provided during this interview.

 

REFERENCE/SOURCE

The Swiss Paraplegic Centre (http:// www.paraplegie.ch), Nottwil, Switzerland.

Choosing the right rehabilitation facility is one of the most important decisions a survivor of a brain or spinal cord injury will make as the type and quality of care will have a significant impact on the patient’s long-term outcome. The top 10 rehabilitation centers in the United States are (http://www.brainandspinalcord.org/2016/04/15/top-ten-rehabilitation-hospitals-usa/):

  1. Rehabilitation Institute of Chicago
  2. TIRR Memorial Hermann
  3. Kessler Institute for Rehabilitation
  4. University of Washington Medical Center
  5. Spaulding Rehabilitation Hospital, Massachusetts General Hospital
  6. Mayo Clinic
  7. Craig Hospital
  8. Shepard Center
  9. Rusk Rehabilitation at NYU Langone Medical Center
  10. Moss Rehab

The Rehabilitation Institute of Chicago (https://www.sralab.org/new-ric), located in Chicago, Illinois, has been ranked as the number one rehabilitation hospital in the United States for the past 24 years by U.S. News and World Report. It is a 182-bed research facility that focuses solely on rehabilitation in many areas, including spinal cord, brain, nerve, muscle and bone, cancer and pediatric. For example, the rehabilitation course for patients with spinal cord injury requires precise medical and nursing expertise, respiratory and pulmonary care and sophisticated diagnostic and therapeutic equipment. For several years, the hospital has dedicated investments in talent, space and equipment that attract a high volume of patients with challenging conditions. The high volume, diversity of condition and greater complexity enables them to expand their experience in helping patients recover from spinal cord injury. Primary goals for patients include the emergence of meaningful motor function, sensation, coordination and endurance, resolution of respiratory and vascular instability, and overall continued medical recovery from the injury or disease.

The Spaulding Rehabilitation Hospital Boston (http://spauldingrehab.org/about/facts-statistics) is ranked number five in the country by U.S. News and World Report and number one in New England.  As a unique center of treatment excellence and a leading physical medicine and rehabilitation research institution, Spaulding Boston is comprised of major departments in all areas of medicine requiring rehabilitation. They are a nationally recognized leader in innovation, research and education.  The facility also has been the source of significant treatment innovations with dramatic implications for a range of conditions, including amputation and limb deficiencies, brain injury, cardiac rehabilitation, pulmonary rehabilitation and spinal cord injuries, to name a few. http://spauldingrehab.org/conditions-and-treatments/list.

Whether individuals are adjusting to a life-altering illness or recovering from a back injury, they will find the care they need within the Spaulding Rehabilitation Network.  Rehabilitation specialists have the training, experience, resources and dedication to help individuals:

  • Regain function after a devastating illness or injury,
  • Develop skills to be active and independent when living with chronic illness and/or disability,
  • Recover from surgery, work and sports injuries, and
  • Grow to the fullest physical, emotional, cognitive and social potential. http://spauldingrehab.org/conditions-and-treatments/

The ACGME accredited Harvard Medical School/ Spaulding/ VA Boston Fellowship Program in  Spinal Cord Injury (SCI) Medicine is a 12-month training program that offers advanced clinical training in SCI, a strong didactic component, and opportunities for research with protected elective time.  The curriculum is designed to provide exposure to the full spectrum of SCI care and includes rotations at VA Boston, Spaulding Rehabilitation Hospital, and Brigham & Woman’s Hospital. Requirements include prior completion of an approved residency program in a specialty such as physical medicine and rehabilitation, neurology, internal medicine, family practice, surgery, or other specialties relevant to spinal cord injury.  http://spauldingrehab.org/education-and-training/spinal-cord-fellowship.

Specifically, the Spaulding Rehabilitation Network is at the forefront of innovative treatment for major disabling conditions, including spinal cord injury (SCI), traumatic brain injury (TBI), other traumatic injuries, stroke, and neuromuscular disorders such as multiple sclerosis, cerebral palsy, and Parkinson’s disease. At Spaulding, the treatment goals go far beyond immediate rehabilitation to address long-term health and function, as well as giving patients encouragement and hope as they return to their lives in the community.

The hub of their spinal cord injury program is the Spaulding-Harvard Spinal Cord Injury Model Systems (SCIMS) Rehabilitation Program, led by experts at Spaulding Boston, a Center of Excellence in spinal cord injury rehabilitation. With the guidance of their  physicians and other rehabilitation specialists and access to some of the most advanced technologies available today, their patients have the resources to strive for their highest level of neurorecovery – and to develop successful, enriching strategies for independent living.

When potentially life-altering spinal cord injury occurs, the Spaulding Rehabilitation Network clinicians are dedicated to pioneering improved therapies that can make all the difference to a patient’s immediate and long-term recovery. Their goal is to support a patient’s return to an active, productive and fulfilling life.

Whether the spinal cord injury is due to traumatic injury or illness, their team of experts will develop a treatment plan in collaboration with the patient and family. Depending on the severity of the injury, their teams work on improving function in: walking, balance and mobility; speech, swallowing and breathing; thinking (cognition), behavior and safety; dressing, bathing and other activities of daily living; incontinence, bowel and bladder function.

Their commitment is to offer a full spectrum of rehabilitation services for adults and children with spinal cord injury:

  • Intensive, hospital-level rehabilitation with goal-directed therapy 3 – 5 hours a day, at least 5 days a week for inpatients.
  • Long-term care and rehabilitation for patients with complicating conditions.
  • Cutting-edge spinal cord injury technologies and therapeutic techniques.
  • Emphasis on family participation throughout the course of care. with an inpatient comprehensive training and education series.
  • Seamless transition to multi-disciplinary outpatient rehabilitation.
  • Coordination of care with Spaulding’s outpatient centers.
  • Vocational training, participation in research, support groups.

Spaulding Rehabilitation Network is the official teaching partner of the Harvard Medical School Department of Physical Medicine and Rehabilitation (PM&R). The Spaulding network’s facilities are members of Partners HealthCare, founded by Massachusetts General Hospital and Brigham and Women’s Hospital. The knowledge and expertise of this entire healthcare system is available to patients and caregivers. Their continuum of superb healthcare ensures that patients will find the care they need throughout their journey and the strength they need to live their life to the fullest.

Other related articles 

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Other related articles were published in this Open Access Online Scientific Journal include the following:

2016

Use of Sensors, Data and Devices to improve Health, San Francisco, April 5-6, 2016: Wearable Tech + Digital Health Conferences

https://pharmaceuticalintelligence.com/2016/01/25/use-of-sensors-data-and-devices-to-improve-health-san-francisco-april-5-6-2016-wearable-tech-digital-health-conferences/

2015

New Spinal Cord Repair Strategy using 3D Cell Growth

https://pharmaceuticalintelligence.com/2015/10/31/new-spinal-cord-repair-strategy-using-3d-cell-growth/

Unsupervised, Mobile and Wireless Brain–Computer Interfaces on the Horizon

https://pharmaceuticalintelligence.com/2015/11/21/unsupervised-mobile-and-wireless-brain-computer-interfaces-on-the-horizon/

Diffuse optics detects spinal cord ischemia – Optics.org

https://pharmaceuticalintelligence.com/2015/05/07/diffuse-optics-detects-spinal-cord-ischemia-optics-org/

Essential for Rehabilitation

https://pharmaceuticalintelligence.com/2015/12/03/essential-for-rehabilitation/

Read Full Post »


Updated: Investing and Inventing: Is the Tango of Mars and Venus Still on

Curator: Aviva Lev-Ari, PhD, RN

UPDATED on 8/18/2014 – Bruce Booth in FORBES

 

VC-Backed Biotech IPOs: Valuations And Virtuous Cycles

 

UPDATED on 8/18/2014

7 Unconventional Ways To Fund A Medtech Startup

By Jim Pomager

Gears and dollars

Bringing innovative new medical technology to market today is as challenging, complex, and competitive an endeavor as it’s ever been for entrepreneurs and startups. Making matters worse, venture capital — the fuel that fledgling companies once depended on to drive product development — has dwindled in recent years.

According to an annual report by PricewaterhouseCoopers (PwC) and the National Venture Capital Association (NVCA), venture capitalists (VCs) invested a mere $2.1 billion in medical device and equipment companies in 2013. That may sound like a lot on the surface, but it’s the lowest annual figure for the industry in the last nine years, down 17 percent from $2.5 billion in 2012, and down a whopping 43 percent from the $3.7-billion high-water mark of 2007.

Not only is funding scarce, but VCs have become incredibly risk averse, waiting until much later in the product development cycle to get involved. There was a time not so long ago when new entrants to the medtech sector could obtain funding with little more than a great idea and a solid business plan, or so it seemed. Today, however, investors are withholding their support until a device accumulates significant safety and efficacy evidence, and often until regulatory and reimbursement approval have been secured. This leads to an unfortunate catch-22 — startups need substantial funding to get their technology into clinical trials, but VCs often want to see clinical trial data before committing.

Faced with this conundrum, medtech entrepreneurs have to get creative, and the broader healthcare industry is rallying to help support them. Experts from Cleveland Clinic, UnitedHealthcare, and other organizations discussed this trend during a lively panel session on this topic called How Healthcare Will Support Startups: In Dollars And Beyond, during the recent MedCity Converge conference in Philadelphia. While the panel focused primarily on digital health startups, they did identify 7 nontraditional sources of funding that might fit the bill for your medical technology company.

1. Divergent Corporate Venturing
Seeking capital from established corporations may not sound like a novel idea. In fact, it has become commonplace for large medical device companies to loan small, private companies millions in return for an option to purchase them at a later date. (See Boston Scientific’s $15 million deal with MValve Technologies last month or St. Jude’s acquisition of CardioMEMS in June.) These arrangements have their benefits — medtech corporations offer startups critical market knowledge and tend to be more patient than private VC firms.

However, more interesting strategic partnerships are beginning to form across traditional industry lines. Not only can large corporations outside the medical device space offer medtech startups new investment streams, they can also provide important technological solutions and a fresh perspective on design. “We are typically looking not just for cash, but for other technologies that our startups can embed in theirs to make a better mousetrap,” said Gary Fingerhut, executive director of Cleveland Clinic Innovations.

Fingerhut’s group, whose goal is to translate the ideas of physicians, scientists, and caregivers to the market, manages approximately 450 royalty-bearing licenses a year from a traditional tech transfer perspective, and also has 67 spinoff companies operating underneath it. Among the many cross-industry corporate partnerships it has helped form for its startups in recent years are joint initiatives with Parker Hannifin, IBM, Verizon, and Lubrizol.

“We very much believe that it can bring a lot of resources to the table — not just capital, but resources in other industries that they’ve been in and have not ventured into healthcare,” Fingerhut added. “We bring the domain expertise. They bring their technologies, their experience, their go-to-market capabilities, and their capital. It’s a win-win.”

2. Aggressive Grant Funding
Another twist on a familiar fundraising tactic was identified by Tom Vanderheyden, VP of business development and commercialization for health insurance carrier UnitedHealthcare (UHC). He said that really focused startups can sometimes substitute significant grant funding in lieu of early VC support.

“Something that I’ve seen a few times recently is companies taking the angel rounds of a couple hundred thousand dollars to get started, and then putting a lot of energy into grant funding,” he said. “They go for the non-dilutive $1 million to $3 million. We’ve seen that be very successful, and then you come out of that grant funding phase and you’ve got meaningful enterprise that’s got lots of IP juice behind it.”

Daphne Zohar, founder of PureTech Ventures — a venture creation company that proactively creates new companies to solve unmet healthcare problems (including one developing a noninvasive neuromodulation device for the treatment of neuropsychiatric disorders) — said that her company pursues a great deal of grants for its startups. “We actually have a person full-time on the team who just applies for grants,” she explained. “They have gotten millions in grants, which is terrific, because the funds are non-dilutive and move things forward.”

Cleveland Clinic’s Fingerhut agreed, saying his group has brought in over $150 million of state money through programs like Ohio’s Third Frontier. Many other states offer similar programs to support startups. (For instance, I wrote about Pennsylvania’s Ben Franklin Technology Partners in a previous story.) The federal government is also a good source of grant money, through the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs at the National Institutes of Health (NIH) and National Science Foundation (NSF).

3. Accelerators & Incubators
Having founded a medtech startup himself, Joseph Mayer, M.D., extolled the virtues of accelerators and incubators. The CEO of Cureatr, a mobile care coordinator, went through the New York Digital Health Acceleratorwhen his company was starting out.

“For us, it was a good opportunity,” he said. “We had two people when we started, with one customer, and we came out of it with two more customers. At the end of the day, that’s what matters. You have to ask yourself, ‘What would I pay for two customers in terms of salespeople, etc.?’”

Compared to some other sources of funding, the amount of money you can get from an accelerator or incubator is relatively small, typically in the tens or hundreds of thousands. UHC’s Vanderheyden said that Rock Health, a healthcare accelerator that his group supports, characterizes its financial support as “grants and Ramen (the infamous and inexpensive instant noodles) money.” But what these entities lack in funds they more than make up for in value-added services.

“We are very active with accelerators in terms of venturing,” said Vanderheyden. “Some entrepreneurs we have found in this space are focused on the clinical benefit, the physician engagement, etc. They haven’t quite figured out yet the economics of the business. That’s something we feel we can shine some light on.” In addition to business advice, some of the perks provided by these programs can include inexpensive office and lab space, medical expertise and guidance, targeted educational programming, and more.

And some accelerators are now offering funding packages that are “getting closer to real money,” as Vanderheyden put it. You can obtain a total of $300,000 from New York Digital Health, he said. Verizon Foundation gives approximately $800,000, according to Cleveland Clinic’s Fingerhut. And there’s nothing prohibiting startups from going through multiple accelerator programs.

4. Partnering With Not-For-Profits
Everyone knows that patient advocacy and other not-for-profit organizations play a major role in financially (and otherwise) backing fundamental research. But what you may not know is that these groups are starting to become much more involved in helping technologies related to their treatment areas of interest reach commercialization.

Zohar described an initiative that PureTech Ventures launched called the Valley of Life, which brings together investors and not-for-profits to achieve common financial and mission-driven goals. The program aims to assist select startups bridge the so-called biomedical “valley of death” between angel and VC funding.

The Valley of Life’s first pilot program is in the juvenile diabetes space and involves the Juvenile Diabetes Research Foundation and the Joslin Diabetes Center (an affiliate of Harvard Medical School). “The idea is basically a $10 million fund that’s funded primarily from patient groups that have been up until now funding basic research, and are now really interested in the translational aspect,” Zohar explained.

5. Customer Investment
The next approach, while admittedly much more straightforward for digital health companies than for pure-play device makers, is still worth noting. Cureatr’s Mayer was the first to point out that customers can be an excellent source of funding for new companies: “You build a strong relationship with a customer, a large health system, the big for-profits in the national market — they’re starting to do more and more, not just biotech but healthcare IT investment.”

In some cases, these current or future customers may be willing to pay an advance on future services. “Another thing I have seen, but I won’t say we’ve done, is what I like to call the prepaid revenue model,” said UHC’s Vanderheyden. “I have seen corporates take some risk and say, ‘I think over the next 12 or 24 months, we plan on spending $600,000 in total for your services, so we’ll give you half of that up front to get the party started. Now you can get some hiring done and expand your infrastructure — whatever you need to do.”

6. Hybrid VC Approaches
Although securing venture capital funding is no picnic these days, there are signs that the situation is improving. According to the latest quarterly report from PwC and NVCA, VC dollars invested in the medical devices and equipment sector rose for the second straight month, reaching $649 million in 73 deals. Narrowing the focus to the capital of the global medical device market, Minnesota saw medical device investing more than double between Q2 2013 and Q2 2014, per a recent report from Life Science Alley.

PureTech’s Zohar shared a potential strategy for working with VC investors — engage a mixture of life science and technology investors, and cater to each group’s specific needs. “I think one thing that’s interesting is the metrics that life science investors use versus the metrics that technology investors use. There really are not many investors that are focused on digital health and can really look at all sides of the spectrum,” she said. “Tech investors tend to look at the customers and whether you have revenue or are likely to have revenue, whereas life science investors will look at the technology IP and the specific application. The kinds of things that we’re doing are really a hybrid, so we have to cultivate a group of investors that have that creativity.”

Regardless of whether you use a traditional approach or a hybrid one, Mayer of Cureatr shared some general advice on engaging the right VC investor. Make sure you pick one that truly understands the healthcare sales cycle, that believes in you and your team, and that you think you will enjoy working with, he suggested.

7. Crowdfunding
The use of crowdfunding was an almost unavoidable topic of discussion. After all, not a week goes by without news of a medtech startup (particularly in the wearable segment) launching a new Kickstarter or Indiegogo campaign. However, I saved it until last because the panel expressed a great deal of concern about the use of crowdfunding, and offered some sound advice as to why.

Vanderheyden shared a cautionary tale, based on an anecdote he heard during a recent investor conference in Minneapolis. “[One of the speakers] said he took over for a company that had crowdfunded. They had 450 non-credited investors, and he said it was a disaster. One of the investors had originally sent in $5,400, and 90 days later he calls the CEO asking for his money back,” Vanderheyden explained. “Think about it as the CEO of an early-stage startup. Now you have dozens and dozens —or conceptually hundreds — of equity stakeholders, non-accredited, that you now have to manage.”

As an inherently public exercise, crowdfunding also exposes startups to potentially negative publicity. Zohar likened it to using an online dating site, where people won’t be willing to engage you until you have built up sufficient credibility and validation on the site. “There’s a bit of a risk in putting yourself out there and saying, ‘Hey, I’m looking for money,’” she said of crowdfunding. “What if you can’t raise the money? What does that say [to potential investors]? Does that say your idea isn’t good?

“During the very early stages, when we actually could use that funding, we would rather find the funding from other sources that exist, and not put ourselves out there as looking like as if we need the money,” she added.

If you are hell-bent on exploring crowdfunding for your startup, the panelists agreed that you should check outAngelList, which is effectively a crowdfunding site for accredited investors. “AngelList is probably the best example of institutionalized crowdfunding,” Mayer said, “where you can get 20 people into a round.”

While finding and obtaining investment for new medtech companies is certainly a challenge in the current economic environment, it is far from impossible, as the examples above attest. I am curious to hear your opinion on these strategies — or other unconventional methods you have either used or learned about. 

SOURCE 

http://www.meddeviceonline.com/doc/seven-unconventional-ways-to-fund-a-medtech-startup-0001?sthash.1CpwsFKh.mjjo

UPDATED on 4/15/2014

14th ANNUAL BIOTECH IN EUROPE FORUM For Global Partnering & Investment
30th September – 1st October 2014 • Congress Center Basel

SACHS Associates, London

http://www.sachsforum.com/zurich14/index.html

UPDATED on 4/15/2014

New Trends in Investing and Inventing: Who Benefits from the Booming Success of the Technology Industry

INVESTMENT BANKING, TECHNOLOGY, VENTURE CAPITAL, INITIAL PUBLIC OFFERINGS, SILICON VALLEY (CALIF), START-UPS

The dealbook.nytimes.com reported in 4/13/2014 the following IPO related and Start up Cases that exemplify the NEW trends

by Sydney Emner with Comments of Scott Kupor, Managing Partner at Andreessen Horowitz.

  • “There’s a broader public policy question here,” Mr. Kupor said. “There is a wealth transfer happening, from public investors to private investors. And the benefits are accruing to the investors that can access the private markets.”
  • Of the 100 largest venture capital rounds on record, 88 were issued within the past five years, according to CrunchBase, which tracks venture funding. Each delivered more than $50 million to the companies.
  • Proliferation of big late-stage investments: The average size of such investments so far this year was $44.1 million, the highest level in the past five years and up 77 percent from last year, according to data from CB Insights.
  • Technology start-ups are staying private longer
  • Venture capital firms are looking to put idle funds to work, and
  • Institutional investors are chasing returns in fast-growing private companies
  • Megarounds, the flood of money is inflating the valuations of early-stage companies. companies are collecting the additional money simply because they can, taking advantage of an ocean of ready cash
  • Over valuations may lead to yet another dot-com bubble 2014 vs 2001
  • For venture capitalists, allowing portfolio companies to take on more funding means their existing stakes can be diluted. But since these big rounds often lead to much higher valuations, many investors don’t mind
  • Partner at Sequoia Capital, conceded that investors were spending less and less time conducting due diligence: playing by slightly different rules than what happened even five years ago
  • In recent years the sheer amount of capital available for investment in Silicon Valley start-ups went up: big venture capital firms have recently raised big rounds, meaning the traditional backers of tech firms are well positioned to write big checks
  • Venture capitalists are increasingly being joined by hedge funds and private equity firms chasing huge returns. Among the top investors in fund-raising rounds that collected over $100 million are
  1. Digital Sky Technologies and
  2. Tiger Global Management, which ranked alongside traditional venture capital firms like
  3. Andreessen Horowitz and
  4. Kleiner Perkins Caufield & Byers, according to CB Insights
  1. T. Rowe Price and
  2. Fidelity Investments.
  3. JPMorgan

“Appreciation that normally would have happened in the public market is happening in the private market,” said Mr. Kupor of Andreessen Horowitz. “This is why we see T. Rowe, Fidelity and JPMorgan investing. They’re saying, ‘There’s not a lot of growth for us in the public market.’ ”

  • In many cases, such firms are given access to promising start-ups with the understanding that they would remain investors even after an I.P.O.
  • Some hedge funds are even transforming themselves into so-called growth capital firms that invest in older start-ups. Coatue Management, for example, is planning on raising a $500 million fund devoted to the kinds of investments that the firm has made in companies like Snapchat.com and the last-minute hotel booking site HotelTonight.comDropbox.com  is another case in point
  • Instead of raising just enough money for the next 18 months or two years, companies are now raising all the money they could feasibly need as a private company in one fell swoop.“Today, companies can raise money well ahead of any actual need.” Mr. Fogelsong said.
  • Companies receiving the influxes of capital, having so much money in the bank allows them to control their own destiny, rather than be at the mercy of acquirers or the markets. “If someone wants to buy them, they can turn it down and wait for a higher price,” said Peter C. Wendell, managing director of Sierra Ventures. “If the I.P.O. is looking shaky, they can say, ‘Look at my balance sheet,’ and wait.”
  • The average age of companies going public today is 10 years, in contrast to the average of just six years in 2000, according to Jay R. Ritter, a professor at the University of Florida.
  • On average, between a quarter and just under a third of the late-stage money is being used to buy shares from employees and early investors ahead of an I.P.O.
  • “Rounds that would have otherwise gotten done in the public markets are getting done in the private markets,” said Scott Kupor, partner and chief operating officer of Andreessen Horowitz, a venture capital firm that is among the most active participants in big late-stage rounds.

Case Study #1: Quora.com

Quora, a question-and-answer website, didn’t need to raise money. It had barely touched $60 million in venture capital that it accepted just two years ago. Yet the California company, which has no revenue and just 70 employees, recently announced that it had raised an additional $80 million. The new round valued the company at a reported $900 million, more than double the previous valuation of $400 million. That means that while some early investors may have seen their ownership diluted by the new round, the value of their holdings nonetheless soared.  “When it goes off at a high price, the V.C. gets to change the price of the other stock on his books,” said Mr. Wendell of Sierra Ventures. The result is that much of a company’s gain in value is happening before it even goes public.

Case Study #2: Nextdoor.com

Silicon Valley expression: Eat when the food is passed,” said Nirav Tolia, chief executive of Nextdoor, which last year accepted $60 million in additional venture funding despite having plenty of money in the bank. . “It’s always good to bet on the furthest-out point.” per Mr. Tolia

Case Study #3: Airbnb.com

Airbnb, the home-sharing site, neared a deal to raise as much as a staggering $500 million from investors like TPG Growth, T. Rowe Price and Dragoneer Investment Group, according to people briefed on the matter. TPG Growth alone had been prepared to provide up to $150 million in the round, one of these people said

Case Study #4: Uber.com and Lyft.com

And two weeks ago, Lyft raised $250 million from the likes of the Alibaba Group of China and Daniel S. Loeb’s investment firm, Third Point — despite being widely regarded as significantly behind the leader in the car service industry, Uber.com

Longer incubation periods mean many companies do need more capital for operating expenses. For example, companies that focus on on-demand services, like the car ride companies Uber and Lyft, require capital as they build out their dispatch networks in new cities and offer new products.

Case Study #5: Fab.com

Fab.com, an e-commerce start-up that raised $150 million last summer at the tender age of two years. An overambitious expansion plan and falling sales led to a wave of employee exits and a painful retrenchment.

Case Study #6: Box.com

Box, the cloud storage company, has filed to go public at a time when, filings show, it needs to raise more capital. But its rival, Dropbox, recently raised $250 million and may put off its I.P.O., especially as appetite for technology stocks is faltering.

Case Study #7: HomeAway.com

In 2008, HomeAway, the real estate website, was planning to go public. But as the financial crisis began, HomeAway executives decided to postpone the I.P.O. Instead, in November of that year, HomeAway raised $250 million in additional venture capital and resolved not to think about going public for at least two years.  The company finally went public in 2011.

SOURCE

http://dealbook.nytimes.com/2014/04/13/rich-start-ups-go-back-for-another-helping/?_php=true&_type=blogs&emc=edit_dlbkam_20140414&nl=business&nlid=40094405&_r=0

 

UPDATED 3/1/2014

The 2nd ANNUAL Sachs Cancer Bio Partnering & Investment Forum Promoting Public & Private Sector Collaboration & Investment in Drug Development, 19th March 2014 • New York Academy of Sciences • USA

https://pharmaceuticalintelligence.com/2013/12/17/the-2nd-annual-sachs-cancer-bio-partnering-investment-forum-promoting-public-private-sector-collaboration-investment-in-drug-development-19th-march-2014-•-new-york-academy-o/#!

 

UPDATED on 1/10/2014

Biotech Showcase™ 2014

January 13-15, 2014 San Francisco, CA Parc 55 Wyndham, SF, Union Square

Program Overview

 

Investing and Inventing: Is the Tango of Mars and Venus Still on

Curator: Aviva Lev-Ari, PhD, RN

According to JERZY GANGISERIAL ENTREPRENEUR

Investing and inventing has become way too dogmatic:

  • Investors say, “We don’t fund ideas, we fund traction.”
  • Entrepreneurs say, “You never make a business plan. You only make an MVP.”
  • Investors say, “We like companies that are going to get acquired for $100M, not try to go for an IPO.”
  • Entrepreneurs say, “I’ll just aim for an acqui-hire or a small M&A deal, it’s much lower risk.”
  • Investors say, “We make a lot of small investments, instead of one or two that are potential home runs.

SOURCE

http://jerzygangi.com/why-silicon-valley-funds-instagrams-not-hyperloops/#!

This curation was conceived following the review on the following Sources:

Source # 1 

WHERE STARTUP FUNDING REALLY COMES FROM (INFOGRAPHIC)

By Laura Entis, November 20, 2013

Posted by Healthios Xchange Administrator Wed at 10:23 AM – 301 views – Filed in Healthios Selections

 

http://www.healthiosxchange.com/articles/1030/where-startup-funding-really-comes-from#!

Source #2

WHY SILICON VALLEY FUNDS INSTAGRAMS, NOT HYPERLOOPS

by JERZY GANGI SERIAL ENTREPRENEUR, August 19, 2013

http://jerzygangi.com/why-silicon-valley-funds-instagrams-not-hyperloops/#!

Source #3

Special Issue: Silicon Valley: Global model or unique anomaly by Social Science Information/SSI – A Sage Publicationsinternational  journal

Reporter: Aviva Lev-Ari, PhD, RN

 
Source #4
 

Innovators can exit with an idea: How to Monetizing Patents and ideas: yazamIP.com launches Idea Lab

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/12/08/innovators-can-exit-with-an-idea-how-to-monetizing-patents-and-ideas-yazamip-com-launches-idea-lab/

Source #5

Connecting INVENTORS to BUSINESS BUILDERS and INVESTORS

Source #6

University-Industry Partnerships; NIH/DOD Funded Industry – Academic Collaborations

According to Source #1: Investing and inventing: Is the Tango of Mars and Venus Still on

Where Startup Funding Really Comes From (Infographic)

According to Source #2: Investing and inventing: Is the Tango of Mars and Venus Still on

Ten Theories explain the REALITY

THEORY 1: THE IPO MARKET SUCKSTHEORY 2: CONTEMPORARY PORTFOLIO STRATEGY FAVORS LAYUPS AND DISCOURAGES 3-POINTERS

THEORY 3: “WE DON’T FUND IDEAS”

THEORY 4: “minimally viable product” The MVP OBSESSION

THEORY 5: THE MARKET REWARDS EXITS, NOT INNOVATION AND VALUETHEORY 6: INVESTORS ARE TOO SPECIALIZED

THEORY 7: MOST ANGELS AND VC’S ARE WIMPS

Second 7 in the Original Article, thus,

  • 2nd 7 = Theory 8
  • Theory 8 = Theory 9
  • Theory 9 = Theory 10

THEORY 7: CORPORATE R&D AND CORPORATE TALENT RETENTION SUCKS, SO CORPORATE M&A IS HUNGRY

THEORY 8: FIRST-TIME ENTREPRENEURS CAN’T BE TRUSTED

THEORY 9: THE REAL REASON IS THAT WE’RE SHEEP

According to Source #3: The SILICON VALLEY Tango of Investing and inventing is Still on

Henry Etzkowitz

Silicon Valley at risk? Sustainability of a global innovation icon: An introduction

to the Special Issue

Social Science Information December 2013 52: 515-538,

doi:10.1177/0539018413501946

Doug Henton and Kim Held

The dynamics of Silicon Valley: Creative destruction and the evolution of the

innovation habitat

Social Science Information December 2013 52: 539-557,

doi:10.1177/0539018413497542

James C Williams

From white gold to silicon chips: Hydraulic technology, electric power and

Silicon Valley

Social Science Information December 2013 52: 558-574,

doi:10.1177/0539018413497834

Annika Steiber and Sverker Alänge

The formation and growth of Google: A firm-level triple helix perspective

Social Science Information December 2013 52: 575-604,

doi:10.1177/0539018413497833

Henry Etzkowitz

StartX and the ‘Paradox of Success’: Filling the gap in Stanford’s

entrepreneurial culture

Social Science Information December 2013 52: 605-627,

doi:10.1177/0539018413498833

Steven Casper

New-technology clusters and public policy: Three perspectives

Social Science Information December 2013 52: 628-652,

doi:10.1177/0539018413501236

Helen Lawton Smith, John Glasson, Saverio Romeo, Rupert Waters, and Andrew

Chadwick

Entrepreneurial regions: Evidence from Oxfordshire and Cambridgeshire

Social Science Information December 2013 52: 653-673,

doi:10.1177/0539018413499978

 

According to Source #4: Investing and inventing: Is the Tango of Mars and Venus Still on

 The IDEA as Entry and as Exit Point
 

1. yazamIP.com launches Idea Lab, enabling innovators to exit without necessarily establishing a startup.

If you: (A) have a track record of innovation and have a solution for a significant technical problem, and (B) are interested in either of the options below, both have no cost to you: (i) a $1,000,000 “exit” from your idea without necessarily leaving your “day-job”; (ii) having proven innovation, patent and business experts work with you to establish a robust patent portfolio based on your idea. And you maintain the option to spin off the strong portfolio into a startup for you to build the market.

Then yazamIP.com’s Idea Lab is for you. See http://www.yazamip.com/valuations

2. Tel Aviv University’s Ramot raises $17m from Tata & SanDisk.http://yazamip.com/node/84

3. Elvis Presley IP sells. http://yazamip.com/node/82

4. Innovation and patents are helping to increase gun sales.http://yazamip.com/node/85

Want to get a valuation on your patent? See http://yazamip.com/valuations

Do not forget to contact yazamIP.com to inquire about our most generous “referral a patent” fee arrangement.

 
NEWS AND DEVELOPMENTS1. yazamIP.com launches patent valuation service. http://www.yazamip.com/valuations2. yazamIP.com client initiates patent infringement action against Sony.http://www.yazamip.com/node/743. Twitter has only 9 patents pre-IPO, a fact that has investors worried.http://www.yazamip.com/node/734. Marijuana-related patents? Now that is a market to corner!http://www.yazamip.com/node/77
SERVICES
  1. If the companies are in distress and have US patents then we can sell them for the inventor
  2. If the patents are being infringed upon, we can see how we can help the inventor get compensated
  3. If the inventors have great ideas that they have not turned into companies yet, we would consider investing in them to convert the ideas into patent portfolios

According to Source #5: Connecting INVENTORS to BUSINESS BUILDERS and INVESTORS — Investing and inventing: Is the Tango of Mars and Venus Still on

National Venture Capital Association <http://www.nvca.org/>
DEN =http://www.den.dartmouth.edu/     http://www.den.dartmouth.edu/about/overview.html
Small Business Investment Companies (SBIC) <http://www.sba.gov/content/venture-capital-startups-high-growth-technology-companies>   programs by state
Directory of Angel-investor networks <http://www.inc.com/articles/2001/09/23461.html>
Tech Coast Venture Network <http://tcvn.org/>
Start-up Report posting service <http://www.startupreport.com/>
Hub Angels Investment Group, LLC <http://www.hubangels.com/>
Links to Angel networks in Midwest <http://www.northstareconomics.com/angel_investing.htm>
The San Diego Venture Group <http://www.sdvg.org/>
Angels in Arizona <http://www.arizonaangels.com/index.htm>
The Aurora Angels <http://www.auroraangels.com/>
Atlanta, Georgia, Angel network <http://angelatlanta.com/>
Valley Angel Investment Fund
<http://gust.com/angel-group/valley-angel-investment-fund> Ohio Angel network <http://www.c-cap.net/about.html>
Great Valley Pennsylvania Angel network <http://www.greatvalleyalliance.com/programs/paan.htm>
Vancouver, British Columbia Angel network <http://www.vef.org/>
Information and links to venture capital sources in China <http://www.chinasite.com/Business/VentureCapital.html>
Los Angeles Regional Technology Alliance <http://www.larta.org/>

According to Source #6:University-Industry Partnerships; NIH/DOD Funded Industry – Academic Collaborations – Investing and inventing: Is the Tango of Mars and Venus Still on

 
 
 
Presentation and Panel Discussion
 
University-Industry Partnerships; NIH/DOD Funded Industry – Academic Collaborations
 

The 9th Annual Non-Dilutive Funding Summit is proud to host Dr. Anthony Boccanfuso, Executive Director, The National Academies’ University-Industry Demonstration Partnership (UIDP) who will discuss in his presentation industry-academic collaborations and how the life science industry can leverage such ties to secure non-diltuive capital to fund their R&D activities.

 
Following the presentation, Dr. Boccanfuso will lead a panel discussion featuring top industry executives who will detail how non-dilutive funding substantially assisted in maintaining a sustainable business while promoting their R&D efforts.
 
 
 – REGISTRATION IS FREE OF CHARGE –
 
1:00 – 2:30
Presentation – University-Industry Partnerships
Presenter and Panel Moderator:
Anthony Boccanfuso
Executive Director, The National Academies’ University-Industry Demonstration Partnership (UIDP)


 
 
 
 
 
 
Panel Discussion
University-Industry Partnerships; NIH/DOD Funded Industry/Academic Collaborations
 
 
Dr. Eric Patzer
Founder and President, Aridis Pharmceuticals
 
 
Dr. Scott Thatcher
CEO & Founder, Orphagen
 
Dr. Timothy A Antaya
CEO, Antaya Science and Technology
 
James Knighton
CEO, AvidBiotics
 
Full Meeting Agenda
07:30 – 08:30
Pre-Conference Workshop – 1X1 RO1 for Companies
Ayal Ronen
Vice President, FreeMind Group
 
 
08:30 – 09:00 Breakfast and Networking  
09:00 – 10:15

Welcome Presentation 

– Non-Dilutive Funding Forecast 2014

 

Ram May-Ron
Managing Partner, FreeMind Group
 
10:30 – 11:30
Keynote – National Heart, Lung, and Blood Institute (NHLBI; NIH) Presentation: “Navigating the Transition from Discovery to Market” 
Dr. Jodi Black
 
Deputy Director, Division of Extramural Research Activities, National Heart, Lung, and Blood Institute, NIH
 
11:30 – 12:00 NIH Round Table Discussion – Meet with NHLBI OfficialsDr.JodiBlackDeputy Director, Division of Extramural Research Activities, National, Heart, Lung, and Blood Institute,NIHLarryMahanDirector, Office of Translational Alliances & Coordination at National Heart, Lung, and Blood Institute, NIH
12:00 – 1:00 Break  
1:00 – 2:30
Presentation – University-Industry Partnerships
Presenter and Panel Moderator:
Anthony Boccanfuso
Executive Director, University-Industry Demonstration Partnership (UIDP)


 
 
 
 
 
 
Panel Discussion
University-Industry Partnerships; NIH/DOD Funded Industry/Academic Collaborations
 
 
Dr. Eric Patzer
Founder and President, Aridis Pharmceuticals
 
 
Dr. Scott Thatcher
CEO & Founder, Orphagen
 
Dr. Timothy A Antaya
CEO, Antaya Science and Technology
 
James Knighton
CEO, AvidBiotics
2:30 – 3:00 Coffee Break  
3:00 – 3:30

Meet the Expert – Round Table Discussions

Neurological Disorders Funding Opportunities
 

Guy Har-Chen
Chief Analyst, FreeMind Group

 
3:30 – 4:00

Meet the Expert – Round Table Discussions

Infectious Diseases and Biodefense Funding Opportunities
Guy Har-Chen
Chief Analyst, FreeMind Group
 
4:00 – 4:30 Closing Remarks  

SOURCE 

This email was sent to avivalev-ari@alum.berkeley.edu by carla@freemindconsultants.com |

FreeMind Group | 423 Brookline Avenue #124 | Boston | MA | 02215 

617-648-0340 ext 249

CONCLUSIONS

by Aviva Lev-Ari, PhD, RN

  • Investing and inventing is a Market Place as well as a Profession. Market places are typified by information imperfection and Professions are typified by very steep Specialization and Competition
  • I am in full agreement with the comment made by

Stephen J. Williams, Ph.D.

Stephen J. Williams, Ph.D, Cancer Pharmacologist, Expert, Author, Writer and Senior Editor @ http;//pharmaceuticalintelligence.com
“Quite interesting that average family and friends investment is $23,000. I wonderhowtheywereabletoseperateoutcrowdfunding, angel investors, from family and friends. I also wonder whattherateofincreasewithcrowdfunding is? However equally surprising is that VC does not make that much of initial startup funding. I think banks level of funding have steadily decreased since the consolidation of the 90’s.”

  • I followed the advice of Dr. Dror Nir and I perfectly agree with his observation on the relevance of the Ten Theories by  JERZY GANGI, SERIAL ENTREPRENEUR

Dror Nir
Dror Nir, Managing partner at RadBee, Expert, Author, Writer, Editor and Top Contributor to LinkedIn Group: Leaders in Pharmaceutical Business Intelligence

“I think you should read this, there are interesting insights which I very much agree with.”
http://jerzygangi.com/why-silicon-valley-funds-instagrams-not-hyperloops/

  • Innovators can exit with an idea: How to Monetizing Patents and ideas: yazamIP.com launches Idea Lab. yazamIP.com launches Idea Lab, enabling innovators to exit without necessarily establishing a startup. This is a desruptive technology with great potential designed to solve problems emerging from the Ten theories of the dogmatic nature of the interplay between Investors and Entrepreneurs who are either the Inventors or the Team members of Start ups.
  • I agree with JERZY GANGI, SERIAL ENTREPRENEUR that Investing and inventing has become way too dogmatic:
    • Investors say, “We don’t fund ideas, we fund traction.”
    • Entrepreneurs say, “You never make a business plan. You only make an MVP.”
    • Investors say, “We like companies that are going to get acquired for $100M, not try to go for an IPO.”
    • Entrepreneurs say, “I’ll just aim for an acqui-hire or a small M&A deal, it’s much lower risk.”
    • Investors say, “We make a lot of small investments, instead of one or two that are potential home runs.
  • Source #1 – is a MUST information to be mastered by both Investors and Entrepreneurs
  • The ten theories are very insightful, they mirror my own views on  Investing and inventing as is manifested in the US and in other Developed countries.
  • Angel Investment is there to stay and is the MOST sensitive source of funding affected by volatility in economic markets conditions. Source #5 was add as an endorsed suggestion made by Dr. Justin D Pearlman, MD, PhD, FACC an Expert, Author, Writer, Editor @ http://pharmaceuticalintelligence.com, a Patent holder and an Inventor at Leaders of Pharmaceutical Business Intelligence
  • Silicon Valley is where I lived, 1978 – 1990 (Palo Alto), pursued Graduate studies (UC, Berkeley, Stanford GSB) and worked as an Executive in the Largest Think Tank in the US, SRI International, and at Amdahl Corporation, Sunnyvale, CA]. The SIlicon Valley is not an anomaly but a Singular point in the Entrepreneurship Ecosystem.
  • Silicon Valley is being followed by another Singular point driven by and derived from a different ethos and impatus, namelythe ecosystem in the “Start ups Nation” Israel.
  • Israel is different than the Silicon Valley in CA, or any other Start ups hub in the US.
  • I am in full agreement, based on my own experience as an Israeli resident in Israel, 1958 – 1978, with the differences and the unique reasons for the Israeli success, as presented  in

Start-up Nation: The Story of Israel’s Economic Miracle by Dan Senor (Author), Saul Singer (Author)
http://www.amazon.com/Start-up-Nation-Israels-Economic-Miracle/dp/0446541478

Other related articles published on this Open Access Online Scientific Journal include the following:

 

Read Full Post »


The Delicate Connection:  IDO (Indolamine 2, 3 dehydrogenase) and Cancer Immunology

Author and Curator: Demet Sag, PhD, CRA, GCP      

Table of Contents:

  1. Abstract
  2. Dual role for IDO
  3. Immune System and IDO
  4. Autoimmune disorders and IDO
  5. Cancer and Ido
  6. Clinical Interventions
  7. Clinical Trials
  8. Future Actions for Molecular Dx and Targeted Therapies:
  9. Conclusion
  10. References

TABLE 1- IDO Clinical Trials

TABLE 2- Kyn induced Genes

TABLE 3 Possible biomarkers and molecular diagnostics targets

TABLE 4: Current Interventions ______________________________________________________________________________________________________________

ABSTRACT:

Overall purpose is to find a method to manipulate IDO for clinical applications, mainly the focus of this review is is cancer prevention and treatment.  The first study proving the connection between IDO and immune response came from, a very natural event, a protection of pregnancy in human. This led to discover that high IDO expression is a common factor in cancer tumors. Thus, attention promoted investigations on IDO’s role in various disease states, immune disorders, transplantation, inflammation, women health, mood disorders.
Many approaches, vaccines and adjuvants are underway to find new immunotherapies by combining the power of DCs in immune response regulation and specific direction of siRNA.  As a result, with this unique qualities of IDO, DCs and siRNA, we orchestrated a novel intervention for immunomodulation of IDO by inhibiting with small interference RNA, called siRNA-IDO-DCvax.  Proven that our DCvax created a delay and regression of tumor growth without changing the natural structure and characterization of DCs in melanoma and breast cancers in vivo. (** The shRNA IDO- DCvax is developed by Regen BioPhrama, San Diego, CA ,  Thomas Ichim, Ph.D, CSO. and David Koos, CEO)

______________________________________________________________________________________________________________

Double-Edged Sword of IDO: The Good and The Bad for Clinical intervention and Developments

IDO almost has a dual role. There is a positive side of high expression of IDO during pregnancy (29; 28; 114), transplants (115; 116; 117; 118; 119), infectious diseases (96) and but this tolerance is negative during autoimmune-disorders (120; 121; 122), tumors of cancer (123; 124; 117; 121; 125; 126; 127) (127), and mood disorders (46). The increased IDO expression has a double-edged sword in human physiology provides a positive role during protection of fetus and grafts after transplantations but becomes a negative factor during autoimmune disorders, cancer, sepsis and mood disorders.

Prevention of allogeneic fetal rejection is possible by tryptophan metabolism (26) rejecting with lack of IDO but allocating if IDO present (29; 28; 114). These studies lead to find “the natural regulation mechanism” for protecting the transplants from graft versus host disease GVHD (128) and getting rid of tumors.

The plasticity of  mammary and uterus during reproduction may hold some more answers to prevent GVHD and tumors of cancer with good understanding of IDO and tryptophan mechanism (129; 130). After allogeneic bone marrow transplants the risk of solid tumor development increased about 80% among 19,229 patients even with a greater risk among patients under 18 years old (117).  The adaptation of tolerance against host mechanism is connected to the IDO expression (131). During implantation and early pregnancy IDO has a role by making CD4+CD25+Foxp3+ regulatory T cells (Tregs) and expressing in DCs and  MQs  (114; 132; 133).

Clonal deletion mechanism prevents mother to react with paternal products since female mice accepted the paternal MHC antigen-expressing tumor graft during pregnancy and rejected three weeks after delivery (134). CTLA-4Ig gene therapy alleviates abortion through regulation of apoptosis and inhibition of spleen lymphocytes (135).  

 Immune System and IDO DCs are the orchestrator of the immune response (56; 57; 58) with list of functions in uptake, processing, and presentation of antigens; activation of effector cells, such as T-cells and NK-cells; and secretion of cytokines and other immune-modulating molecules to direct the immune response. The differential regulation of IDO in distinct DC subsets is widely studied to delineate and correct immune homeostasis during autoimmunity, infection and cancer and the associated immunological outcomes. Genesis of antigen presenting cells (APCs), eventually the immune system, require migration of monocytes (MOs), which is originated in bone marrow. Then, these MOs move from bloodstream to other tissues to become macrophages and DCs (59; 60).

Initiation of immune response requires APCs to link resting helper T-cell with the matching antigen to protect body. DCs are superior to MQs and MOs in their immune action model. When DCs are first described (61) and classified, their role is determined as a highly potent antigen-presenting cell (APC) subset with 100 to 1000-times more effective than macrophages and B-cells in priming T-cells. Both MQs and monocytes phagocytize the pathogen, and their cell structure contains very large nucleus and many internal vesicles. However, there is a nuance between MQ and DCs, since DCs has a wider capacity of stimulation, because MQs activates only memory T cells, yet DCs can activate both naïve and memory T cells.

DCs are potent activators of T cells and they also have well controlled regulatory roles. DC properties determine the regulation regardless of their origin or the subset of the DCs. DCs reacts after identification of the signals or influencers for their inhibitory, stimulatory or regulatory roles, before they express a complex repertoire of positive and negative cytokines, transmembrane proteins and other molecules. Thus, “two signal theory” gains support with a defined rule.  The combination of two signals, their interaction with types of cells and time are critical.

In short, specificity and time are matter for a proper response. When IDO mRNA expression is activated with CTL40 ligand and IFNgamma, IDO results inhibition of T cell production (4).  However, if DCs are inhibited by 1MT, an inhibitor of IDO, the response stop but IgG has no affect (10).  In addition, if the stimulation is started by a tryptophan metabolite, which is downstream of IDO, such as 3-hydroxyantranilic or quinolinic acids, it only inhibits Th1 but not Th2 subset of T cells (62).

Furthermore, inclusion of signal molecules, such as Fas Ligand, cytochrome c, and pathways also differ in the T cell differentiation mechanisms due to combination, time and specificity of two-signals.  The co-culture experiments are great tool to identify specific stimuli in disease specific microenvironment (63; 12; 64) for discovering the mechanism and interactions between molecules in gene regulation, biochemical mechanism and physiological function during cell differentiation.

As a result, the simplest differential cell development from the early development of DCs impact the outcome of the data. For example, collection of MOs from peripheral blood mononuclear cells (PBMCs) with IL4 and GM-CSF leads to immature DCs (iDCs). On next step, treatment of iDCs with tumor necrosis factor (TNF) or other plausible cytokines (TGFb1, IFNgamma, IFNalpha,  IFNbeta, IL6 etc.) based on the desired outcome differentiate iDCs  into mature DCs (mDCs). DCs live only up to a week but MOs and generated MQs can live up to a month in the given tissue. B cells inhibit T cell dependent immune responses in tumors (65).

AutoImmune Disorders:

The Circadian Clock Circuitry and the AHR

The balance of IDO expression becomes necessary to prevent overactive immune response self-destruction, so modulation in tryptophan and NDA metabolisms maybe essential.  When splenic IDO-expressing CD11b (+) DCs from tolerized animals applied, they suppressed the development of arthritis, increased the Treg/Th17 cell ratio, and decreased the production of inflammatory cytokines in the spleen (136).

The role of Nicotinamide prevention on type 1 diabetes and ameliorates multiple sclerosis in animal model presented with activities of  NDAs stimulating GPCR109a to produce prostaglandins to induce IDO expression, then these PGEs and PGDs converted to the anti-inflammatory prostaglandin, 15d-PGJ(2) (137; 138; 139).  Thus, these events promotes endogenous signaling mechanisms involving the GPCRs EP2, EP4, and DP1 along with PPARgamma. (137).

Modulating the immune response at non-canonical at canonocal pathway while keeping the non-canonical Nf-KB intact may help to mend immune disorders. As a result, the targeted blocking in canonical at associated kinase IKKβ and leaving non-canonocal Nf-kB pathway intact, DCs tips the balance towards immune supression. Hence, noncanonical NF-κB pathway for regulatory functions in DCs required effective IDO induction, directly or indirectly by endogenous ligand Kyn and negative regulation of proinflammatory cytokine production. As a result, this may help to treat autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, and multiple sclerosis, or allergy or transplant rejection.

While the opposite action needs to be taken during prevention of tumors, that is inhibition of non-canonical pathway.  Inflammation induces not only relaxation of veins and lowering blood pressure but also stimulate coagulopathies that worsen the microenvironment and decrease survival rate of patients after radio or chemotherapies.Cancer Generating tumor vaccines and using adjuvants underway (140).

Clinical correlation and genetic responses also compared in several studies to diagnose and target the system for cancer therapies (127; 141; 131).  The recent surveys on IDO expression and human cancers showed that IDO targeting is a candidate for cancer therapy since IDO expression recruiting Tregs, downregulates MHC class I and creating negative immune microenvironment for protection of development of tumors (125; 27; 142).  Inhibition of IDO expression can make advances in immunotherapy and chemotherapy fields (143; 125; 131; 144).

IDO has a great importance on prevention of cancer development (126). There are many approaches to create the homeostasis of immune response by Immunotherapy.  However, given the complexity of immune regulations, immunomodulation is a better approach to correct and relieve the system from the disease.  Some of the current IDO targeted immunotherapy or immmunomodulations with RNA technology for cancer prevention (145; 146; 147; 148; 149; 150) or applied on human or animals  (75; 151; 12; 115; 152; 9; 125) or chemical, (153; 154) or  radiological (155).  The targeted cell type in immune system generally DCs, monocytes (94)T cells (110; 156)and neutrophils (146; 157). On this paper, we will concentrate on DCvax on cancer treatments.

 T-reg, regulatory T cells; Th, T helper; CTLA-4, cytotoxic T lymphocyte-associated antigen 4; TCR, T cell receptor; IDO, indoleamine 2,3-dioxygenase. (refernece: http://www.pnas.org/content/101/28/10398/suppl/DC)

T-reg, regulatory T cells; Th, T helper; CTLA-4, cytotoxic T lymphocyte-associated antigen 4; TCR, T cell receptor; IDO, indoleamine 2,3-dioxygenase. (refernece: http://www.pnas.org/content/101/28/10398/suppl/DC)

IDO and the downstream enzymes in tryptophan pathway produce a series of immunosuppressive tryptophan metabolites that may lead into Tregs proliferation or increase in T cell apoptosis (62; 16; 27; 158), and some can affect NK cell function (159).

The interesting part of the mechanism is even without presence of IDO itself, downstream enzymes of IDO in the kynurenine tryptophan degradation still show immunosuppressive outcome (160; 73) due to not only Kyn but also TGFbeta stimulated long term responses. DC vaccination with IDO plausible (161) due to its power in immune response changes and longevity in the bloodstream for reversing the system for Th17 production (162).

Clinical Interventions are taking advantage of the DC’s central role and combining with enhancing molecules for induction of immunity may overcome tolerogenic DCs in tumors of cancers (163; 164).

The first successful application of DC vaccine used against advanced melanoma after loading DCs with tumor peptides or autologous cell lysate in presence of adjuvants keyhole limpet hematocyanin (KLH) (165).  Previous animal and clinical studies show use of DCs against tumors created success (165; 166; 167) as well as some problems due to heterogeneity of DC populations in one study supporting tumor growth rather than diminishing (168).

DC vaccination applied onto over four thousand clinical trial but none of them used siRNA-IDO DC vaccination method. Clinical trials evaluating DCs loaded ex vivo with purified TAAs as an anticancer immunotherapeutic interventions also did not include IDO (Table from (169). This table presented the data from 30 clinical trials, 3 of which discontinued, evaluating DCs loaded ex vivo with TAAs as an anticancer immunotherapy for 12 types of cancer [(AML(1), Breast cancer (4), glioblastoma (1), glioma (2), hepatocellular carcinoma (1), hematological malignancies (1), melanoma (6), neuroblastoma sarcoma (2), NSCLC (1), ovarian cancer (3), pancreatic cancer (3), prostate cancer (10)] at phase I, II or I/II.

Tipping the balance between Treg and Th17 ratio has a therapeutic advantage for restoring the health that is also shown in ovarian cancer by DC vaccination with adjuvants (161).  This rebalancing of the immune system towards immunogenicity may restore Treg/Th17 ratio (162; 170) but it is complicated. The stimulation of IL10 and IL12 induce Treg produce less Th17 and inhibiting CTL activation and its function (76; 171; 172) while animals treated with anti-TGFb before vaccination increase the plasma levels of IL-15 for tumor specific T cell survival in vivo (173; 174) ovarian cancer studies after human papilloma virus infection present an increase of IL12 (175).

Opposing signal mechanism downregulates the TGFb to activate CTL and Th1 population with IL12 and IL15 expression (162; 173).  The effects of IL17 on antitumor properties observed by unique subset of CD4+ T cells (176) called also CD8+ T cells secrete even more IL17 (177).

Using cytokines as adjuvants during vaccination may improve the efficacy of vaccination since cancer vaccines unlike infections vaccines applied after the infection or disease started against the established adoptive immune response.  Adjuvants are used to improve the responses of the given therapies commonly in immunotherapy applications as a combination therapy (178).

Enhancing cancer vaccine efficacy via modulation of the microenvironment is a plausible solution if only know who are the players.  Several molecules can be used to initiate and lengthen the activity of intervention to stimulate IDO expression without compromising the mechanism (179).  The system is complicated so generally induction is completed ex-vivo stimulation of DCs in cell lysates, whole tumor lysates, to create the microenvironment and natural stimulatory agents. Introduction of molecules as an adjuvants on genetic regulation on modulation of DCs are critical, because order and time of the signals, specific location/ tissue, and heterogeneity of personal needs (174; 138; 180). These studies demonstrated that IL15 with low TGFb stimulates CTL and Th1, whereas elevated TGFb with IL10 increases Th17 and Tregs in cancer microenvironments.

IDO and signaling gene regulation

For example Ret-peptide antitumor vaccine contains an extracellular fragment of Ret protein and Th1 polarized immunoregulator CpG oligonucleotide (1826), with 1MT, a potent inhibitor of IDO, brought a powerful as well as specific cellular and humoral immune responses in mice (152).

The main idea of choosing Ret to produce vaccine in ret related carcinomas fall in two criterion, first choosing patients self-antigens for cancer therapy with a non-mutated gene, second, there is no evidence of genetic mutations in Ret amino acids 64-269. Demonstration of proliferating hemangiomas, benign endothelial tumors and often referred as hemangiomas of infancy appearing at head or neck, express IDO and slowly regressed as a result of immune mediated process.

After large scale of genomic analysis show insulin like growth factor 2 as the key regulator of hematoma growth (Ritter et al. 2003). We set out to develop new technology with our previous expertise in immunotherapy and immunomodulation (181; 182; 183; 184), correcting Th17/Th1 ratio (185), and siRNA technology (186; 187).  We developed siRNA-IDO-DCvax. Patented two technologies “Immunomodulation using Altered DCs (Patent No: US2006/0165665 A1) and Method of Cancer Treatments using siRNA Silencing (Patent No: US2009/0220582 A1).

In melanoma cancer DCs were preconditioned with whole tumor lysate but in breast cancer model pretreatment completed with tumor cell lysate before siRNA-IDO-DCvax applied. Both of these studies was a success without modifying the autanticity of DCs but decreasing the IDO expression to restore immunegenity by delaying tumor growth in breast cancer (147) and in melanoma (188).  Thus, our DCvax specifically interfere with Ido without disturbing natural structure and content of the DCs in vivo showed that it is possible to carry on this technology to clinical applications.

Furthermore, our method of intervention is more sophisticated since it has a direct interaction mechanism with ex-vivo DC modulation without creating long term metabolism imbalance in Trp/Kyn metabolite mechanisms since the action is corrective and non-invasive.

There were several reasons.

First, prevention of tumor development studies targeting non-enzymatic pathway initiated by pDCs conditioned with TGFbeta is specific to IDO1 (189).

Second, IDO upregulation in antigen presenting cells allowing metastasis show that most human tumors express IDO at high levels (123; 124).

Third, tolerogenic DCs secretes several molecules some of them are transforming growth factor beta (TGFb), interleukin IL10), human leukocyte antigen G (HLA-G), and leukemia inhibitory factor (LIF), and non-secreted program cell death ligand 1 (PD-1 L) and IDO, indolamine 2.3-dioxygenase, which promote tumor tolerance. Thus, we took advantage of DCs properties and Ido specificity to prevent the tolerogenicity with siRNA-IDO DC vaccine in both melanoma and breast cancer.

Fourth, IDO expression in DCs make them even more potent against tumor antigens and create more T cells against tumors. IDOs are expressed at different levels by both in broad range of tumor cells and many subtypes of DCs including monocyte-derived DCs (10), plasmacytoid DCs (142), CD8a+ DCs (190), IDO compotent DCs (17), IFNgamma-activated DCs used in DC vaccination.  These DCs suppress immune responses through several mechanisms for induction of apoptosis towards activated T cells (156) to mediate antigen-specific T cell anergy in vivo (142) and for enhancement of Treg cells production at sites of vaccination with IDO-positive DCs+ in human patients (142; 191; 192; 168; 193; 194). If DCs are preconditioned with tumor lysate with 1MT vaccination they increase DCvax effectiveness unlike DCs originated from “normal”, healthy lysate with 1MT in pancreatic cancer (195).  As a result, we concluded that the immunesupressive effect of IDO can be reversed by siRNA because Treg cells enhances DC vaccine-mediated anti-tumor-immunity in cancer patients.

Gene silencing is a promising technology regardless of advantages simplicity for finding gene interaction mechanisms in vitro and disadvantages of the technology is utilizing the system with specificity in vivo (186; 196).  siRNA technology is one of the newest solution for the treatment of diseases as human genomics is only producing about 25,000 genes by representing 1% of its genome. Thus, utilizing the RNA open the doors for more comprehensive and less invasive effects on interventions. Thus this technology is still improving and using adjuvants. Silencing of K-Ras inhibit the growth of tumors in human pancreatic cancers (197), silencing of beta-catenin in colon cancers causes tumor regression in mouse models (198), silencing of vascular endothelial growth factor (VGEF) decreased angiogenesis and inhibit tumor growth (199).

Combining siRNA IDO and DCvax from adult stem cell is a novel technology for regression of tumors in melanoma and breast cancers in vivo. Our data showed that IDO-siRNA reduced tumor derived T cell apoptosis and tumor derived inhibition of T cell proliferation.  In addition, silencing IDO made DCs more potent against tumors since treated or pretreated animals showed a delay or decreased the tumor growth (188; 147)

 

Clinical Trials:

First FDA approved DC-based cancer therapies for treatment of hormone-refractory prostate cancer as autologous cellular immunotherapy (163; 164).  However, there are many probabilities to iron out for a predictive outcome in patients.

Table 2 demonstrates the current summary of clinical trials report.  This table shows 38 total studies specifically Ido related function on cancer (16), eye (3), surgery (2), women health (4), obesity (1), Cardiovascular (2), brain (1), kidney (1), bladder (1), sepsis shock (1), transplant (1),  nervous system and behavioral studies (4), HIV (1) (Table 4).  Among these only 22 of which active, recruiting or not yet started to recruit, and 17 completed and one terminated.

Most of these studies concentrated on cancer by the industry, Teva GTC ( Phase I traumatic brain injury) Astra Zeneca (Phase IV on efficacy of CRESTOR 5mg for cardiovascular health concern), Incyte corporation (Phase II ovarian cancer) NewLink Genetics Corporation Phase I breast/lung/melanoma/pancreatic solid tumors that is terminated; Phase II malignant melanoma recruiting, Phase II active, not recruiting metastatic breast cancer, Phase I/II metastatic melanoma, Phase I advanced malignancies) , HIV (Phase IV enrolling by invitation supported by Salix Corp-UC, San Francisco and HIV/AIDS Research Programs).

Many studies based on chemotherapy but there are few that use biological methods completed study with  IDO vaccine peptide vaccination for Stage III-IV non-small-cell lung cancer patients (NCT01219348), observational study on effect of biological therapy on biomarkers in patients with untreated hepatitis C, metastasis melanoma, or Crohn disease by IFNalpha and chemical (ribavirin, ticilimumab (NCT00897312), polymorphisms of patients after 1MT drug application in treating patients with metastatic or unmovable refractory solid tumors by surgery (NCT00758537), IDO expression analysis on MSCs (NCT01668576), and not yet recruiting intervention with adenovirus-p53 transduced dendric cell vaccine , 1MT , radiation, Carbon C 11 aplha-methyltryptophan- (NCT01302821).

Among the registered clinical trials some of them are not interventional but  observational and evaluation studies on Trp/Kyn ratio (NCT01042847), Kyn/Trp ratio (NCT01219348), Kyn levels (NCT00897312, NCT00573300),  RT-PCR analysis for Kyn metabolism (NCT00573300, NCT00684736, NCT00758537), and intrinsic IDO expression of mesenchymal stem cells in lung transplant with percent inhibition of CD4+ and CD8+ T cell proliferation toward donor cells (NCT01668576), determining polymorphisms (NCT00426894). These clinical trials/studies are immensely valuable to understand the mechanism and route of intervention development with the data collected from human populations   

Future Actions for Molecular Dx and Targeted Therapies:

Viable tumor environment. Tumor survival is dependent upon an exquisite interplay between the critical functions of stromal development and angiogenesis, local immune suppression and tumor tolerance, and paradoxical inflammation. TEMs: TIE-2 expressing monocytes; “M2” TAMs: tolerogenic tumor-associated macrophages; MDSCs: myeloid-derived suppressor cells; pDCs: plasmacytoid dendritic cells; co-stim.: co-stimulation; IDO: indoleamine 2,3-dioxygenase; VEGF: vascular endothelial growth factor; EGF: epidermal growth factor; MMP: matrix metaloprotease; IL: interleukin; TGF-β: transforming growth factor-beta; TLRs: toll-like receptors.  (reference: http://www.hindawi.com/journals/cdi/2012/937253/fig1/)

Viable tumor environment. Tumor survival is dependent upon an exquisite interplay between the critical functions of stromal development and angiogenesis, local immune suppression and tumor tolerance, and paradoxical inflammation. TEMs: TIE-2 expressing monocytes; “M2” TAMs: tolerogenic tumor-associated macrophages; MDSCs: myeloid-derived suppressor cells; pDCs: plasmacytoid dendritic cells; co-stim.: co-stimulation; IDO: indoleamine 2,3-dioxygenase; VEGF: vascular endothelial growth factor; EGF: epidermal growth factor; MMP: matrix metaloprotease; IL: interleukin; TGF-β: transforming growth factor-beta; TLRs: toll-like receptors. (reference: http://www.hindawi.com/journals/cdi/2012/937253/fig1/)

Current survival or response rate is around 40 to 50 % range.  By using specific cell type, selected inhibition/activation sequence based on patient’s genomic profile may improve the efficacy of clinical interventions on cancer treatments. Targeted therapies for specific gene regulation through signal transduction is necessary but there are few studies with genomics based approach.

On the other hand, there are surveys, observational or evaluations (listed in clinical trials section) registered with www.clinicaltrials.gov that will provide a valuable short-list of molecules.  Preventing stimulation of Ido1 as well as Tgfb-1gene expression by modulating receptor mediated phosphorylation between TGFb/SMAD either at Mad-Homology 1 (MH1) or Mad-Homology 1 (MH2) domains maybe possible (79; 82; 80). Within Smads are the conserved Mad-Homology 1 (MH1) domain, which is a DNA binding module contains tightly bound Zinc atom.

Smad MH2 domain is well conserved and one the most diverse protein-signal interacting molecule during signal transduction due to two important Serine residues located extreme distal C-termini at Ser-Val-Ser in Smad 2 or at pSer-X-PSer in RSmads (80). Kyn activated orphan G protein–coupled receptor, GPR35 with unknown function with a distinct expression pattern that collides with IDO sites since its expression at high levels of the immune system and the gut (63) (200; 63).  

The first study to connect IDO with cancer shows that group (75).  The directly targeting to regulate IDO expression is another method through modulating ISREs in its promoter with RNA-peptide combination technology. Indirectly, IDO can be regulated through Bin1 gene expression control over IDO since Bin1 is a negative regulator of IDO and prevents IDO expression.  IDO is under negative genetic control of Bin1, BAR adapter–encoding gene Bin1 (also known as Amphiphysin2). Bin1 functions in cancer suppression since attenuation of Bin1 observed in many human malignancies (141; 201; 202; 203; 204; 205; 206) .  Null Bin-/- mice showed that when there is lack of Bin1, upregulation of IDO through STAT1- and NF-kB-dependent expression of IDO makes tumor cells to escape from T cell–dependent antitumor immunity.

This pathway lies in non-enzymatic signal transducer function of IDO after stimulation of DCs by TGFb1.  The detail study on Bin1 gene by alternative spicing also provided that Bin1 is a tumor suppressor.  Its activities also depends on these spliced outcome, such as  Exon 10, in muscle, in turn Exon 13 in mice has importance in role for regulating growth when Bin1 is deleted or mutated C2C12 myoblasts interrupted due to its missing Myc, cyclinD1, or growth factor inhibiting genes like p21WAF1 (207; 208).

On the other hand alternative spliced Exon12A contributing brain cell differentiation (209; 210). Myc as a target at the junction between IDO gene interaction and Trp metabolism.  Bin1 interacts with Myc either early-dependent on Myc or late-independent on Myc, when Myc is not present. This gene regulation also interfered by the long term signaling mechanism related to Kynurenine (Kyn) acting as an endogenous ligand to AHR in Trp metabolite and TGFb1 and/or IFNalpha and IFNbeta up regulation of DCs to induce IDO in noncanonical pathway for NF-kB and myc gene activations (73; 74).  Hence, Trp/Kyn, Kyn/Trp, Th1/Th17 ratios are important to be observed in patients peripheral blood. These direct and indirect gene interactions place Bin1 to function in cell differentiation (211; 212; 205).

Regulatory T-cel generation via reverse and non-canonical signaliing to pDCs

Table 3 contains the microarray analysis for Kyn affect showed that there are 25 genes affected by Kyn, two of which are upregulated and 23 of them downregulated (100). This list of genes and additional knowledge based on studies creating the diagnostics panel with these genes as a biomarker may help to analyze the outcomes of given interventions and therapies. Some of these molecules are great candidate to seek as an adjuvant or co-stimulation agents.  These are myc, NfKB at IKKA, C2CD2, CREB3L2, GPR115, IL2, IL8, IL6, and IL1B, mir-376 RNA, NFKB3, TGFb, RelA, and SH3RF1. In addition, Lip, Fox3P, CTLA-4, Bin1, and IMPACT should be monitored.

In addition, Table 4 presents the other possible mechanisms. The highlights of possible target/biomarkers are specific TLRs, conserved sequences of IDO across its homologous structures, CCR6, CCR5, RORgammat, ISREs of IDO, Jak, STAT, IRFs, MH1 and MH2 domains of Smads. Endothelial cell coagulation activation mechanism and pDC maturation or immigration from lymph nodes to bloodstream should marry to control not only IDO expression but also genesis of preferred DC subsets. Stromal mesenchymal cells are also activated by these modulation at vascular system and interferes with metastasis of cancer. First, thrombin (human factor II) is a well regulated protein in coagulation hemostasis has a role in cell differentiation and angiogenesis.

Protein kinase activated receptors (PARs), type of GPCRs, moderate the actions. Second, during hematopoietic response endothelial cells produce hematopoietic growth factors (213; 214). Third, components of bone marrow stroma cells include monocytes, adipocytes, and mesenchymal stem cells (215). As a result, addressing this issue will prevent occurrence of coagulapathologies, namely DIC, bleeding, thrombosis, so that patients may also improve response rate towards therapies. Personal genomic profiles are powerful tool to improve efficacy in immunotherapies since there is an influence of age (young vs. adult), state of immune system (innate vs. adopted or acquired immunity). Table 5 includes some of the current studies directly with IDO and indirectly effecting its mechanisms via gene therapy, DNA vaccine, gene silencing and adjuvant applications as an intervention method to prevent various cancer types.

CONCLUSION

IDO has a confined function in immune system through complex interactions to maintain hemostasis of immune responses. The genesis of IDO stem from duplication of bacterial IDO-like genes.  Inhibition of microbial infection and invasion by depleting tryptophan limits and kills the invader but during starvation of trp the host may pass the twilight zone since trp required by host’s T cells.  Thus, the host cells in these small pockets adopt to new microenvironment with depleted trp and oxygen poor conditions. Hence, the cell metabolism differentiate to generate new cellular structure like nodules and tumors under the protection of constitutively expressed IDO in tumors, DCs and inhibited T cell proliferation.

On the other hand, having a dichotomy in IDO function can be a potential limiting factor that means is that IDOs impact on biological system could be variable based on several issues such as target cells, IDO’s capacity, pathologic state of the disease and conditions of the microenvironment. Thus, close monitoring is necessary to analyze the outcome to prevent conspiracies since previous studies generated paradoxical results.

Current therapies through chemotherapies, radiotherapies are costly and effectiveness shown that the clinical interventions require immunotherapies as well as coagulation and vascular biology manipulations for a higher efficacy and survival rate in cancer patients. Our siRNA and DC technologies based on stem cell modulation will provide at least prevention of cancer development and hopefully prevention in cancer.

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152. Prevention of Spontaneous Tumor Development in a ret Transgenic Mouse Model by Ret Peptide Vaccination with Indoleamine 2,3-Dioxygenase Inhibitor 1-Methyl Tryptophan. Zeng, J., Cai, S., Yi, Y., et al. 2009, Cancer Res., pp. 69: 3963-3970,  http://dx.doi.org:/10.1158/0008-5472.CAN-08-2476.

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154. Synthesis of 4-cyano and 4-nitrophenyl 1,6-dithio-D-manno-, L-ido- and D-glucoseptanosides possessing antithrombotic activity. Bozó E, Gáti T, Demeter A, Kuszmann J. 2002, Carbohydr Res. , pp. 3;337(15):1351-65.

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159. The tryptophan catabolite L-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function. . Chiesa, M.D., et al. 2006, Blood. , pp. 108:4118–4125.38.

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171. IFNgamma promotes generationof Il-10 secreting CD4+ T cells that suppress generationof CD8responses in an antigen-experienced host. Liu, X.S., Leerberg, J., MacDonald, K., Leggatt, G.R., Frazer, I.H. 2009, J. Immunol., pp. 183: 51-58.

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175. IL-12 enhances CTL synapse formationand induces self-reactivity. Markinewicz, MA, Wise, EL, Buchwald, ZS et al. 2009, J. Immunol., pp. 182: 1351-1362.

176. Tumor specific Th17-polarized cells eradicate large established melanoma. Muranski, P., Boni, A., Antony, PA, et al. 2008, Blood, pp. 112; 362-373.

177. Type17 CD8+ T cells dispplay enhanced antitumor immunity. Hinrichs, C.S., Kaiser, A., Paulos, C.M., et al. 2008, Blood., pp. 112:362-373.

178. Marying Immunotherapy with Chemotherapy: Why Say IDO? Muller, AJ, and Prendergrast, GC. 2005, Cancer Research, pp. 65: 8065-8068.

179. Enhancing Cancer Vaccine efficacy via Modulationof the Tumor Environment. Disis, ML. 2009, Clin Cancer Res, pp. 15: 6476-6478.

180. Systemic inhibition of transforming growth factor beta 1 in glioma bearing mice improves the therapeutic efficacy of glioma-associated antigen peptide vaccines. Ueda, R., Fujita, M., Zhu, X., et al. 2009, Clin. Cancer res., pp. 15: 6551-9.

181. Immune modulation by silencing IL-12 productionin dendritic cells using smal interfering RNA. Hill, JA, Ichim, TE, Kusznieruk, KP, et al. 2003, J. Immunol, pp. 171:809-813.

182. Immune modulation and tolerance induction by RelB-silenced dentritic cells through RNA interference. Li, M. Zang, X, Zheng, X, et al. 2007, J. Immunol, pp. 178: 5480-7.

183. RNAi mediated CD40-CD54 interruption promotes tolerance in autoimmune arthritis. . Zheng, X., Suzuki, M., Zhang, X., et al. 2010, Arthritis Res. Ther., p. 12:R13.

184. Dendritic cells genetically engineered to express Fas ligand induce donor-specific hyporesponsiveness and prolong allograft survival. Min, WP. Gorczynki, R., huang, XY et al. 2000, J. Immunol., pp. 164:161-167.

185. LF15-0195 generates tolerogenic dendritic cells by supressionof NF-kappaB signaling through inhibitionof IKK activity. . Yang, J., Bernier, SM, Ichim, TE, et al. 2003, J Leukoc. Biol., pp. 74: 438-447.

186. RNA interfrence: A potent tool for gene specific therapeutics. . Ichim, TE, Li, M., Qian, H., Popov, HI, Rycerz, K., Zheng, X., White, D., Zhong, R., and Min, WP. 2004, Am. J. Transplant, pp. 4:1227-1236.

187. A novel in vivo siRNA delivery system specifically targeting dendritic cells and silencing CD40 genes for immunomodulation. Zheng, X., Vladau, C., Zhang, X. et al. 2009, Blood, pp. 113:2646-2654.

188. Reinstalling Antitumor Immunity by Inhibiting Tumor derived ImmunoSupressive Molecule IDO through RNA interference. Zheng, X et al. 2006, Int. Journal of Immunology., pp. 177:5639-5646.

189. Roles of TGFbeta in metastasis. Padua, D., Massague, J. 2009, Cell Res., pp. 19;89-102.

190. Functional expression of indolamine2,3-dioxygenase by murine CDalpha+dendritic cells. Fallarino, F., Vacca, C, Orabona, C et al. 2002, Int Immunol., pp. 14:65-8.

191. Indolamine2,3-dioxygenase controls conversion of Fox3+ Tregs to TH17-like cells in tumor draining lymph nodes. Sharma, MD, Hou, DY, Liu, Y et al. 2009, Blood, pp.113: 6102-11.

192. IDO upregulates regulatory T cells via tryptoophan catabolite and supresses encephalitogenic T cell responses in experimental autoimmune encephalomyelitis. Yan, Y, Zhang, GX, Gran, B et al. 2010, J Immunol, pp. 185; 5953-61.

193. IDO activates regulatory T cells and blocks their conversion into Th-17-like T cells. Baban, B, Chandler, PR, Sharma, MD et al. 2009, J Immunol, pp. 183; 2475-83.

194. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletionof regulatory T cells. Dannull, J., Farrand, KJ, Mathews, SA, et al. 2005, J Clin Invest, pp. 115: 3623-33.

195. 1-MT enhances potency of tumor cell lysate pulled dentritic cells against pancreatic adenocarcinoma by downregulating percentage of Tregs. Li, Y, Xu, J, Zhou, H. et al. 2010, J Huazhong Univ Sci Technol Med Sci , pp. 30: 344-8.

196. siRNA mediated antitumorigenesis for drug target validation and therapeutics. Lu, PY, Xie, FY and Woodle, MC. 2003, Curr Opin Mol. Ther., pp. 5:225-234.

197. Stable supression of tumorigenicity by virus-mediated RNA interference. Brumellkamp, TR, Bernards, R, Agami, R. 2002, Cancer Cell, pp. 2; 243-247.

198. Small interferring RNAs directed against beta-catenin inhibit the in vitro and in vivo growth of colon cancer cells. Verma, UN, Surabhi, RM, Schmaltieg, A., Becerra, C., Gaynor, RB. 2003, Clin. Cancer. Res., pp. 9:1291-1300.

199. siRNA mediated inhibition of vascular endothelial growth factor severely limits tumor resistance to antiangiogeneic thromboposdin-1 and slows tumor vascularization and growth. Filleur, S., Courtin, A, Ait-Si-Ali, S., Guglielmi, J., Merel, C., Harel-Bellan, A., CLezardin, P., and Cabon, F. 2003, Cancer Res, pp. 63; 3919-3922.

200. Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35. . Wang, J., et al. 2006, J. Biol.Chem. , pp. 281:22021–22028. 201. Bin1 functionally interacts with Myc in cells and inhibits cell proliferation by multiple mechanisms. Elliott, K. et al. 1999, Oncogene , pp. 18, 3564−3573 .

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203. Losses of the tumor suppressor Bin1 in breast carcinoma are frequent and reflect deficits in a programmed cell death capacity. Ge, K. et al. 2000, Int. J. Cancer , pp. 85, 376−383.

204. Loss of heterozygosity and tumor suppressor activity of Bin1 in prostate carcinoma. Ge, K. et al. 2000, Int. J. Cancer , pp. 86, 155−161.

205. Expression of a MYCN-interacting isoform of the tumor suppressor BIN1 is reduced in neuroblastomas with unfavorable biological features. . Tajiri, T. et al. 2003, Clin. Cancer Res., pp. 9, 3345−3355.

206. Targeted deletion of the suppressor gene Bin1/Amphiphysin2 enhances the malignant character of transformed cells. Muller, A.J., DuHadaway, J.B., Donover, P.S., Sutanto-Ward, E. & Prendergast, G.C. 2004, Cancer Biol. Ther. , p. 3.

207. Interactions of myogenic factors and the retinoblastoma protein mediates muscle commitment and cell differentiation. Gu, WJ., Scheniider,W., Condrolli,G., Kaushal,, S, Mahdavi,V., Nadal-Gnard, B. 1993, Cell, pp. 72; 309-324.

208. Structural analysis of the human BIN1 gene: evidence of tissue-specific transcriptional regualtion and alternate splicing. Wechsler-Reya, R, Sakamuro, J., Zhang, J., DuHadaway, J., and Predengast. 1998, J of Biol Chem.

209. A role for th ePutative Tuimor Supressor Bin1 in Muscle Differentiation. Wechsler-Reya, R., Elliott, KJ, Prendergast, GC. 1998, Molecular and Cellular Biology, p. 18 (1) :566.

210. The putative tumor repressor BIN1 is a short lived nuclear phosphoprotein whose localization is altered in malignant cells. Wechsler-Reya, R., Elliot, K., Herlyn, M., Prendergast, GC. 1997, Cancer Res, pp. 57: 3258-3263.

211. Transformation selective apoptosis by farnesyltransferase inhibitors requires Bin1. DuHadaway, J.B. et al. 2003, Oncogene, pp. 22, 3578−3588 (2003).

212. The c-Myc-interacting adapter protein Bin1 activates a caspase-independent cell death program. Elliott, K., Ge, K., Du, W. & Prendergast, G.C. 2000., Oncogene , pp. 19, 4669−4684.

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214. Exogenous endothelial cells as accelerators of hematopoietic reconstitution. Mizer, C., Ichim, TE, Alexandrescu, DT, DAsanu, CA, Ramos, F., Turner, A., Woods, EJ, Bogon, V., Murphy, MP, Koos, D., and Patel, A. 2013, J. Translational Medicine, p. 10: 231.

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Cardio-Metabolic Drug Targets, Inaugural, September 25 – 26, 2013, Westin Waterfront | Boston, Massachusetts  

 

Reporter: Aviva Lev-Ari, PhD, RN

                                 

ABOUT THIS CONFERENCE

Cardiovascular disease, diabetes, obesity and dyslipidemia, though traditionally treated as separate entities, are often conditions that appear together in individuals because of defects in underlying metabolic processes. Researchers are therefore now seeking compounds that target biological points of intersection of these related diseases in the hopes of ‘killing more birds with one stone.’ Or they are approaching drug development of a compound for a specific disease with a greater awareness of the backdrop of related conditions.

Join fellow biomedical researchers from academia and industry at our day and a half conference, Cardio-Metabolic Drug Targets to discuss the impact of this paradigm change in the way drugs are discovered and developed in the cardio-metabolic arena and to stay abreast of the latest targets and drug development candidates in the pipeline.

SUGGESTED EVENT PACKAGE:

September 23: Allosteric Modulators of GPCRs Short Course 
September 24 – 25: Novel Strategies for Kinase Inhibitors Conference
September 25: Setting Up Effective Functional Screens Using 3D Cell Cultures Dinner Short Course
September 25 – 26: Cardio-Metabolic Drug Targets Conference

Scientific Advisory Board:

Jerome J. Schentag, Pharm.D., Professor of Pharmaceutical Sciences, University at Buffalo

Rebecca Taub, M.D., Ph.D., CEO, Madrigal Pharmaceuticals

Preliminary Agenda

BEYOND STATINS: NEW APPROACHES FOR REGULATING LIPID METABOLISM AND ATHEROSCLEROSIS

Macrophage ABC Transporters: Novel Targets to Promote Atherosclerotic Plaque Regression by Inducing Reverse Cholesterol Transport (RCT) Mechanism

Eralp “Al” Bellibas, M.D., Senior Director, Head, Clinical Pharmacology, The Medicines Company

Targeting PCSK9 for Hypercholesterolemia and Atherosclerosis

Hong Liang, Ph.D., Associate Research Fellow, Rinat Research Unit, Pfizer

Novel Treatment for Dyslipidemia: Liver-Directed Thyroid Hormone Receptor-ß Agonist

Rebecca Taub, M.D., Ph.D., CEO, Madrigal Pharmaceuticals

CARDIO-METABOLIC THERAPEUTIC CANDIDATES

Oral Mimetics of RYGB and GLP-1 in Metabolic Syndromes

Jerome J. Schentag, Pharm.D., Professor of Pharmaceutical Sciences, University at Buffalo

FGF21-Mimetic Antibodies for Type 2 Diabetes

Jun Sonoda, Ph.D., Group Leader, Scientist, Molecular Biology, Genentech

NEW CARDIO-METABOLIC TARGETS

Blockade of Delta-Like Ligand 4 (Dll4)-Notch Signaling Reduces Macrophage Activation and Attenuates Atherosclerotic Vascular Diseases and Metabolic Disorders

Masanori Aikawa, Ph.D., Assistant Professor, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical

Modulating Glycerolipid Metabolism in Myeloid Cells for Cardiometabolic Benefit

Suneil K. Koliwad, M.D., Ph.D., Assistant Professor, Diabetes Center/Department of Medicine, University of California San Francisco

AMPK as a Target in Lipid and Carbohydrate Metabolism

Ajit Srivastava, Ph.D., Adjunct Professor, Pharmacology, Drexel University; Independent Consultant, Integrated Pharma Solutions, LLC

 http://www.discoveryontarget.com/Cardio-Drug-Targets

Inaugural n September 25 – 26, 2013

Cardio-Metabolic Drug Targets

Targeting One, Treating More

»»Suggested Event Package

September 23: Allosteric Modulators of GPCRs Short Course 4

September 24-25: Novel Strategies for Kinase Inhibitors

Conference

September 25: Setting Up Effective Functional Screens Using 3D

Cell Cultures Dinner Short Course 9

September 25-26: Cardio-Metabolic Drug Targets Conference

Wednesday, September 25

11:50 am Registration

BEYOND STATINS: NEW APPRO ACHES FOR

REGULATING LIPID METABOLISM AND

ATHERO SCLERO SIS

1:30 pm Chairperson’s Opening Remarks

1:40 PLENARY KEYNOTE PRESENTATION: Towards a Patient-

Based Drug Discovery

Stuart L. Schreiber, Ph.D., Director, Chemical Biology and Founding Member, Broad

Institute of Harvard and MIT; Howard Hughes Medical Institute Investigator; Morris

Loeb Professor of Chemistry and Chemical Biology, Harvard University

3:10 Refreshment Break in the Exhibit Hall with Poster Viewing

4:00 FEATURED SPEAKER: Atherosclerosis and Cardio-

Metabolism Research Overview: Promising Targets

Margrit Schwarz, Ph.D., MBA, formerly Director of Research, Dyslipidemia and

Atherosclerosis, Amgen; currently President, MS Consulting, LLC

4:30 Sponsored Presentations (Opportunities Available)

5:00 Novel Treatment for Dyslipidemia: Liver-Directed Thyroid

Hormone Receptor-ß Agonist

Rebecca Taub, M.D., Ph.D., CEO, Madrigal Pharmaceuticals

5:30 Modulating Glycerolipid Metabolism in Myeloid Cells for

Cardiometabolic Benefit

Suneil K. Koliwad, MD., Ph.D. Assistant Professor, Diabetes Center/Department

of Medicine, University of California San Francisco (UCSF)

6:00 Targeting PCSK9 for Hypercholesterolemia and

Atherosclerosis

Hong Liang, Ph.D., Associate Research Fellow, Rinat Research Unit, Pfizer

6:30 Close of Day

Thursday, September 26

7:30 am Registration

NEW ARTHERO /LIPID/CARDIO-METABOLIC

DRUG TARGETS

8:00 Breakfast Interactive Breakout Discussion Groups

9:05 Chairperson’s Opening Remarks

9:10 ApoE derived ABCA1 agonists for the Treatment of

Cardiovascular Disease

Jan Johansson, M.D., Ph.D., CEO, Artery Therapeutics, Inc.

9:40 Blockade of Delta-Like Ligand 4 (Dll4)-Notch Signaling

Reduces Macrophage Activation and Attenuates Atherosclerotic

Vascular Diseases and Metabolic Disorders

Masanori Aikawa, Ph.D., Assistant Professor, Department of Medicine,

Brigham and Women’s Hospital and Harvard Medical

10:10 Coffee Break in the Exhibit Hall with Poster Viewing

10:55 AMPK as a Target in Lipid and Carbohydrate Metabolism

Ajit Srivastava, Ph.D., Adjunct Professor, Department of Pharmacology, Drexel

University; Independent Consultant, Integrated Pharma Solutions, LLC

11:25 Macrophage ABC Transporters: Novel Targets to Promote

Atherosclerotic Plaque Regression by Inducing Reverse

Cholesterol Transport (RCT) Mechanism

Eralp “Al” Bellibas, M.D., Senior Director, Head, Clinical Pharmacology, The

Medicines Company

11:55 Targeting Ubiquitin Signaling Mediated Disease Pathology

of LDL Receptors

Udo Maier, Ph.D., Head of Target Discovery Research, Boehringer Ingelheim

Pharma

12:25 pm Sponsored Presentation (Opportunity Available)

12:55 Luncheon Presentation (Sponsorship Opportunity Available) or

Lunch on Your Own

Cardio-Metab olic Mimetics

2:25 Chairperson’s Opening Remarks

2:30 Oral Mimetics of RYGB and GLP-1 in Metabolic Syndromes

Jerome J. Schentag, PharmD, Professor of Pharmaceutical Sciences, University

at Buffalo

3:00 FGF21-Mimetic Antibodies for Type 2 Diabetes

Jun Sonoda, Ph.D., Group Leader, Scientist, Molecular Biology, Genentech

3:30 Ice Cream Refreshment Break in the Exhibit Hall with Poster

Viewing

gpCrS IN METABOLIC DISEASES

4:00 Targeting the Ghrelin Receptor with an Oral, Macrocyclic

Agonist

Helmut Thomas, Ph.D., Senior Vice President, Research and Preclinical

Development, Tranzyme Pharma

4:30 Presentation to be Announced

5:00 Lactate Receptor, GPR81/HCA1, as a Novel Target for

Metabolic Disorders

Changlu Liu, Ph.D., Scientific Director, Janssen Fellow, Head of Molecular

Innovation, Neuroscience, Janssen Research & Development, LLC

5:30 Targeting GPR55 in Cancer and Diabetes

Marco Falasca, Ph.D., Professor of Molecular Pharmacology, Queen Mary

University of London

6:00 Close of Conference

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Larry H Bernstein, MD, FCAP
Pharmaceutical Intelligence

Clinical Trials Revisited

https://pharmaceuticalintelligence.com/2013/04/03/clinical-trials-revisit/

Cancer Clinical Trials of Tomorrow

Advances in genomics and cancer biology will alter the design of human cancer studies

By Tomasz M. Beer | April 1, 2013   The Scientist
We stand on the cusp of significant change in the fundamental structure of cancer clinical trials, as the emphasis begins to shift from large-scale studies of relatively unselected patients to smaller studies testing more narrowly targeted therapies in molecularly characterized populations.
The previous (and still current) generation of trials established the cancer treatment standards used today. Trials that demonstrated the value of combination chemotherapy in the adjuvant treatment of breast cancer are an excellent example. Meticulous development of treatment regimens through Phase 1 and Phase 2 trials, followed by large-scale comparisons of the new regimens to established treatment protocols, have defined the modern practice of oncology for the last 4 decades. Future cancer clinical trials will be very different from those of the past, adopting a more personalized, sometimes called “precision,” approach.
It is, of course, not entirely true that past clinical trials did not include efforts to target treatments to the right patients. Where possible, targeted therapies are already being implemented. Using the presence of endocrine receptors to guide endocrine therapy for breast cancer was one of the first forays into molecular selection of patients. Unfortunately, the ability to select subgroups of patients for study has been severely curtailed by a still-limited knowledge of human cancer biology.
This is rapidly changing, however, thanks to advances in genomics and comprehensive cancer biology research over the last decade. Large-scale efforts, such as The Cancer Genome Atlas, are comprehensively defining many of the crucial molecular characteristics of human malignancies by illuminating genetic alterations that are clinically and biologically important, and which, by virtue of their functional roles, are viable targets for cancer treatment. At the same time, the ability to design small-molecule inhibitors of specific cancer targets is rapidly accelerating. In 2011, two new agents exemplified the power of these trends: crizotinib was approved for the treatment of lung cancers that harbor a specific mutation in the ALK gene, and vemurafenib was approved for the treatment of melanomas with a specific BRAF mutation. In both cases, the drugs were approved along with companion diagnostic tests that identify patients with the target mutation, who are therefore likely to benefit from treatment.

Smaller, more precise trials ahead

Clinical trials are being transformed by these trends. It will not happen overnight, as the knowledge of cancer biology and the availability of targeted agents are uneven. Unselected populations of patients will still be studied, but it is inevitable that there will be a rise in the number of trials that incorporate molecular tumor testing prior to treatment, with treatment selection informed by the molecular features of each individual’s cancer. Such personalized trials have the potential to yield better outcomes by increasing the probability of response and to employ less toxic therapies by increasingly targeting cancer-specific functions, rather than normal proliferative functions.
To the extent that targeted therapies will prove more effective when given to selected patients, clinical trials should get dramatically smaller. Trial size is largely driven by how effective the treatment is expected to be, so fewer participants are needed when the therapeutic benefit is larger. But the promise of smaller trials will not to be universal; for example, when two targeted agents are compared to one another in the same molecularly selected population, the differences in efficacy may be small and larger trials will be required.
As approaches to cancer treatment advance, there will need to be continual engagement with patients and with cancer survivors.
Furthermore, smaller trials may not necessarily move faster or be easier to complete, as they will require the “right patients,” who may be hard to find. Many of the mutations that represent promising targets are present in a minority of tumors. Today, molecular characterization of tumors is often done as part of the screening process for each trial. Many, and sometimes most, of the patients prove ineligible, making this approach frustrating and difficult to carry out. A better avenue of attack would be to make comprehensive molecular characterization of tumors a routine part of establishing a patient’s eligibility for a range of therapies. With the plummeting cost of genomic analysis, one can envision a day in the near future when a complete cancer genome (and perhaps other molecular evaluations) becomes a standard component of an initial diagnostic evaluation. Patients will be armed with molecular information about their own tumors, and thus able to make more-informed decisions about standard and investigational therapies that match the mutations driving their cancer.

New challenges

The road to personalized and targeted treatment strategies will offer new challenges. For rare targets that are present in a minority of cases across many different types of cancers, one will have to consider clinical trials that include a number of different cancers. There are many design pitfalls to such trials, chiefly the additional clinical and molecular heterogeneity introduced by the inclusion of more than one cancer type. Despite these challenges, it will inevitably make sense in some settings to select patients who share a particular tumor biology, regardless of the tissue of origin.
Another major challenge is how to combine targeted therapies to improve clinical outcomes. To date, targeted therapies have not been able to cure advanced solid tumors. Clinical benefits, while sometimes quite impressive when compared to marginally effective treatments, still fall far short. It stands to reason that redundant survival and growth pathways enable tumors to overcome therapies that inhibit a single target. The simultaneous inhibition of relevant redundant pathways may yield dramatically better results, but will also dramatically increase the complexity of molecularly personalized clinical trials.
As approaches to cancer treatment advance, there will need to be continual engagement with patients and with cancer survivors. Fewer than 5 percent of adult cancer patients participate in a clinical trial. To carry out meaningful clinical trials in the future, that number must increase. This will be most important for treatments that target relatively rare mutations; a large number of potential volunteers will have to be screened to identify a sufficient number who harbor the relevant target. To succeed, we must partner with a much larger fraction of cancer patients.
Designing and executing future cancer clinical trials will not be easy, but physician-scientists are armed with a fast-growing body of omics-informed knowledge with which to surmount these hurdles.
Tomasz M. Beer is deputy director of the Knight Cancer Institute and a professor of medicine at Oregon Health & Science University in Portland. He is the coauthor of Cancer Clinical Trials: A Commonsense Guide to Experimental Cancer Therapies and Clinical Trials. Written for people living with cancer, the book is accompanied by a blog (www.cancer-clinical-trials.com) that seeks to disseminate knowledge about clinical trials.

Tags

tumor suppression, tumor heterogeneity, genetics & genomics, disease/medicine, clinical trials, chemotherapy, cancer genomics and cancer

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Rheumatoid Arthritis Risk

Reporter: Larry H Bernstein, MD, FCAP

Liu Y, Aryee MJ, Padyukov L, et al.
Nat Biotechnol. 2013 Jan 20;31(2):142-7.   http://dx.doi.org/10.1038/nbt.2487. Epub 2013 Jan 20.
The concordance rate for identical twins is only 12%-15%, which tells us that
  • other influences are even more important.
  • the “dark matter” of disease risk might be found in epigenetics,
  • defined as heritable changes in the genome without changes in DNA sequences.

Epigenome-wide association data implicate DNA methylation.
http://www.medscape.com//view-article/778573

Genetics of Rheumatic Disease – Medscape: Medical News, Full …Common variants at CD40 and other loci confer risk of rheumatoid arthritis. …
EF, Lee AT, Padyukov L, Alfredsson L, Coblyn J, et al.: … MM, Klei L, Daly MJ …www.medscape.com/viewarticle/717475  
High impact publications – Ongoing research – Karolinska …
Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis
Liu Y, Aryee MJ, Padyukov L, Fallin MD …
http://www.ki.se/ki/jsp/polopoly.jsp?d=7324&a=61979&l=en
Arthritis Research & Therapy
… Seldin MF, Remmers EF, Lee AT, Padyukov L, Alfredsson L, Coblyn J, et al.: … other loci confer risk of rheumatoid arthritis. Nat …
Liu Y, Helms C , Liao W, Zaba LC …   http://www.arthritis-research.com/content/12/3/r116
CHEST Journal
TRAF1-C5 as a risk locus for rheumatoid arthritis—a genomewide ... Liu G; et al . Whole-genome …
Padyukov L; et al. MHC2TA is associated with http://www. journal.publications.chestnet.org/article.aspx?articleid=1086542
Arthritis Research & Therapy 2010, 12:R116 Published: 16 June 2010    http://dx.doi.org/10.1186/ar3053
The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/12/3/R116
JE Hollis-Moffatt, M Chen-Xu, R Topless, N Dalbeth, … and TR Merriman

Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TENR-IL2-IL21 locus in Caucasian sample sets:

Genetic associations implicate aberrant activation and regulation of autoreactive T-cells as central to RA. In addition to the established human leukocyte antigen locus DRB1, other genes more recently confirmed (either through wide replication or combined analysis at a genome-wide level of significance, P ≤ 10-8) as playing a role in the development of RA are the protein

Aside from HLA-DRB1 and PTPN22, the effects are weak (odds ratio (OR) < 1.3). Most of these loci are also implicated as risk factors in other autoimmune phenotypes [12].
There is extensive linkage disequilibrium across the region,

  • hampering fine-mapping efforts [13],
  • there are two independent autoimmune associated regions within the KIAA1109-TENR-IL2-IL21 gene cluster.
We aimed to consolidate all available data on two SNPs independently associated with autoimmunity within the KIAA1109-TENR-IL2-IL21 gene cluster:
  • rs6822844 (minor allele protective) and rs17388568 (minor allele susceptible),
each into a single meta-analysis of association with RA that included previously published data, new genotype data from Australasia, and
publicly-available data from the Wellcome Trust Case Control Consortium (WTCCC).
 The single nucleotide polymorphism (SNP) rs6822844 within the KIAA1109-TENR-IL2-IL21 gene cluster
  • has been associated with rheumatoid arthritis (RA).

Other variants within this cluster, including

  • rs17388568 that is not in linkage disequilibrium (LD) with rs6822844, and
  • rs907715 that is in moderate LD with rs6822844 and rs17388568, have been associated with a number of autoimmune phenotypes,
    • including type 1 diabetes (T1D).

Here we aimed to:

  1. confirm at a genome-wide level of significance association of rs6822844 with RA
  2. evaluate whether or not there were effects independent of rs6822844 on RA at the KIAA1109-TENR-IL2-IL21 locus.

confirmation of association of rs6822844 with rheumatoid arthritis at a genome-wide level of significance

A total of 842 Australasian RA patients and 1,115 controls of European Caucasian ancestry were

  • genotyped for rs6822844, rs17388568 and rs907715.

Meta-analysis of these data with published and publicly-available data was conducted using STATA.
Imputed RA and control genotypes were obtained for

  • rs6822844, rs17388568 and rs907715 from 100% of the WTCCC dataset (1,856 cases, 2,933 controls) using the publicly available WTCCC data
    • using the program IMPUTE [25] and HapMap (NCBI Build 36 (db126b)) CEU data as reference haplotype set.

Of the Australasian case sample set, 99.1% of subjects for rs6822844, 99.1% of subjects for rs17388568 and 98.9% of subjects for rs9077015 were successfully genotyped and, for the 505 member control sample set, 97.4% of subjects for rs6822844, 99.4% of subjects for rs17388568 and 99.4% of subjects for rs9077015 were successfully genotyped. The remaining New Zealand control genotypes (n = 610) were obtained from the genome-wide data, with 100% successfully genotyped for rs17388568 and 99.6% imputed for rs6822844 and rs907715.
Testing for departures from Hardy-Weinberg equilibrium, for the significance of any difference in minor allele frequencies between patients and controls, calculating odds ratios and conditional association testing was done using the PLINK software package. Logistic regression analysis was applied to the Australasian case-control sample set to stratify data according to gender, RF, CCP and SE status using the STATA 8.0 data analysis and statistics software package (StataCorp, College Station, Texas, USA). Meta-analysis was done using the STATA 8.0 metan software package and cumulative P- values reported. The Mantel-Haenszel test was used to estimate the average conditional common odds ratio between these two independent cohorts and to test for heterogeneity between the groups. P- values from the North American Rheumatoid Arthritis Consortium (NARAC) study, which could not be combined using meta-analysis owing to unavailability of allele counts, were combined using Fisher’s method.

No statistically significant evidence for association was observed in the Australasian sample set for rs6822844 (odds ratio (OR) = 0.95 (0.80 to 1.12), P = 0.54), or rs17388568 (OR = 1.03 (0.90 to 1.19), P = 0.65) or rs907715 (OR = 0.98 (0.86 to 1.12), P = 0.69). When combined in a meta-analysis using data from a total of 9,772 cases and 10,909 controls

  • there was a genome-wide level of significance supporting association of rs6822844 with RA (OR = 0.86 (0.82 to 0.91), P = 8.8 × 10-8, P = 2.1 × 10-8 including NARAC data).

Meta-analysis of rs17388568, using a total of 6,585 cases and 7,528 controls, revealed

  • no significant association with RA (OR = 1.03, (0.98 to 1.09); P = 0.22) and
  • meta-analysis of rs907715 using a total of 2,689 cases and 4,045 controls revealed a
  • trend towards association (OR = 0.93 (0.87 to 1.00), P = 0.07).
    • this trend wasnot independent of the association at   rs6822844.

Zhernakova et al. [21] and Coenen et al. [28] both reported association of the KIAA1109-TENR-IL2-IL21 region with RA in overlapping Dutch case-control cohorts. We used data from the former study, as it was the only one to type rs6822844. The meta-analysis provided very strong (genome-wide) support

  • for rs6822844 playing a role in the development of RA (OR = 0.86 (0.82 to 0.91), P = 8.8 × 10-8).

The NARAC GWAS data (OR rs6822844 = 0.84 (0.74-0.96), P = 0.011) [7] were combined with the meta-analysis result, yielding P = 2.1 × 10-8.

The KIAA1109-TENR-IL2-IL21 gene cluster, that encodes aninterleukin (IL-21)that plays an important role in Th17 cell biology, is the

  • 20th locus for which there is a genome-wide (P ≤ 5 ×10-8) level of support for association with RA.

As for most other autoimmune diseases, with the notable exception of T1D, rs6822844 is the dominant association in the locus. The KIAA1109-TENR-IL2-IL21 locus also

    • confers susceptibility to other autoimmune phenotypes with a heterogeneous pattern of association.

 

Genetic “Tags” Linked with RA Risk
Chemical “tags” that attach to DNA and regulate the activity of genes

  • appear to play a role in the development of rheumatoid arthritis.
    1. These results were published in Nature Biotechnology.
Genes play an important role in rheumatoid arthritis (RA) and many other common chronic diseases, but often do not tell the entire story. Factors that regulate the activity of genes are also thought to be important.

    • These factors include chemical tags that bind to DNA.
If the tagging of certain genes is found to contribute to a disease, it could point to news ways to treat the disease. One of the challenges in studying these tags, however, is

  • determining the sequence of events;
  • some tags may occur prior to disease and influence disease development,
  • while other tags may occur as a result of the disease.
To explore genes and their chemical tags in relation to RA,

  • researchers conducted a study among a group of people with RA and a comparison group of people without RA.
  • The researchers were able to identify DNA sites that were tagged differently in people with RA and that appeared to affect the risk of RA.
  • Most of these sites were in an area of the genome that has been linked with autoimmune disease.
In a prepared statement, the senior author of the study summarized the importance of these findings for patients: “Since RA is a disease in which the body’s immune system turns on itself,

    • current treatments often involve suppressing the entire immune system, which can have serious side effects.

The results of this study may allow clinicians to instead directly target the culpable genes and/or their tags.”

Reference: Liu Y, Aryee MJ, Padyukov L et al. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nature Biotechnology. Early online publication January 20, 2013;
New Risk Gene for Rheumatoid Arthritis and Lupus Opens Door to More Effective Treatments
gene variant on STAT4 on chromosome 2
http://phys.org/news108298062/
Study identifies genetic risk factor for rheumatoid arthritis, lupus Sept 6, 2007
A genetic variation has been identified that increases the risk of two chronic, autoimmune inflammatory diseases: rheumatoid arthritis (RA) and systemic lupus erythematosus (lupus).
These research findings result from a long-time collaboration between the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and other organizations.
These results appear in the Sept. 6 issue of the New England Journal of Medicine.
“Although both diseases are believed to have a strong genetic component, identifying the relevant genes has been extremely difficult,” says study coauthor Elaine Remmers, Ph.D.  Dr. Remmers and her colleagues
  • tested variants within 13 candidate genes located in a region of chromosome 2,
  • which they had previously linked with RA,
  • for association with disease in large collections of RA and lupus patients and controls.

Among the variants were several disease-associated single nucleotide polymorphisms (SNPs) —

  • small differences in DNA sequence that represent the most common genetic variations between individuals —
  • in a large segment of the STAT4 gene.

The STAT4 gene encodes a protein that plays an important role in the regulation and activation of certain cells of the immune system.

“It may be too early to predict the impact of identifying the STAT4 gene as a susceptibility locus for rheumatoid arthritis — whether the presence of the variant and others will serve as

  • a predictor of disease,
  • disease outcome or
  • response to therapy,”
says coauthor and NARAC principal investigator Peter K. Gregersen, M.D., of The Feinstein Institute for Medical Research,  in Manhasset, N.Y.

  • “It also remains to be found whether the STAT4 pathway plays such a crucial role in RA and lupus that
  • new therapies targeting this pathway would be effective in these and perhaps other autoimmune diseases.”

One variant form of the gene was present at a significantly higher frequency in RA patient samples from the North American Rheumatoid Arthritis Consortium (NARAC) as compared with controls.
The scientists replicated that result in two independent collections of RA cases and controls. The researchers also found that the same variant of the STAT4 gene was

  • even more strongly linked with lupus in three independent collections of patients and controls.

Frequency data on the genetic profiles of the patients and controls suggest that individuals who carry two copies of the disease-risk variant form of the STAT4 gene have a 60 percent increased risk for RA and more than double the risk for lupus compared with people who carry no copies of the variant form. The research also suggests

  • a shared disease pathway for RA and lupus.

“For this complex disease, rheumatoid arthritis, this is the first instance of a genetic linkage study

  1. leading to a chromosomal location, which then,
  2. in a genetic association study, identified a disease susceptibility gene,” says Dr. Gregersen.

The study’s success, according to NIAMS Director Stephen I. Katz, M.D., Ph.D., can be attributed in part to the uncommon and longstanding collaboration between NIAMS intramural researchers and other scientists the Institute supports around the country. “This work required the collection and genotyping of thousands of RA and lupus cases and controls, a task that would have been difficult to accomplish without the strong partnerships we forged,” he says. NARAC was established 10 years ago by Dr. Gregersen, NIAMS Clinical Director and Genetics and Genomics Branch Chief Daniel Kastner, M.D., Ph.D., and investigators at several academic health centers to facilitate the collection and analysis of RA genetic samples. Adds Dr. Remmers,

“Although we do not yet know precisely how the disease-associated variant of the STAT4 gene increases the risk for developing RA or lupus,
  • it is very exciting to know that this gene plays a fundamental role in these important autoimmune diseases.
” Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases
English: A hand affected by rheumatoid arthritis

English: A hand affected by rheumatoid arthritis (Photo credit: Wikipedia)

Rheumatoid arthritis (1)

Rheumatoid arthritis (1) (Photo credit: Wikipedia)

Typisches Röntgenbild einer Rheumatoiden Arthr...

Typisches Röntgenbild einer Rheumatoiden Arthritis. (Photo credit: Wikipedia)

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