Funding, Deals & Partnerships: BIOLOGICS & MEDICAL DEVICES; BioMed e-Series; Medicine and Life Sciences Scientific Journal – http://PharmaceuticalIntelligence.com
IBM Releases Novel AI-Powered Technologies to Help Health and Research Community Accelerate the Discovery of Medical Insights and Treatments for COVID-19
IBM Research has been actively developing new cloud and AI-powered technologies that can help researchers across a variety of scientific disciplines accelerate the process of discovery. As the COVID-19 pandemic unfolds, we continue to ask how these technologies and our scientific knowledge can help in the global battle against coronavirus.
Today, we are making available multiple novel, free resources from across IBM to help healthcare researchers, doctors and scientists around the world accelerate COVID-19 drug discovery: from gathering insights, to applying the latest virus genomic information and identifying potential targets for treatments, to creating new drug molecule candidates.
Though some of the resources are still in exploratory stages, IBM is making them available to qualifying researchers at no charge to aid the international scientific investigation of COVID-19.
Healthcare agencies and governments around the world have quickly amassed medical and other relevant data about the pandemic. And, there are already vast troves of medical research that could prove relevant to COVID-19. Yet, as with any large volume of disparate data sources, it is difficult to efficiently aggregate and analyze that data in ways that can yield scientific insights.
To help researchers access structured and unstructured data quickly, we are offering a cloud-based AI research resource that has been trained on a corpus of thousands of scientific papers contained in the COVID-19 Open Research Dataset (CORD-19), prepared by the White House and a coalition of research groups, and licensed databases from the DrugBank, Clinicaltrials.gov and GenBank. This tool uses our advanced AI and allows researchers to pose specific queries to the collections of papers and to extract critical COVID-19 knowledge quickly. Please note, access to this resource will be granted only to qualified researchers. To learn more and request access, please click here.
Aiding the Hunt for Treatments
The traditional drug discovery pipeline relies on a library of compounds that are screened, improved, and tested to determine safety and efficacy. In dealing with new pathogens such as SARS-CoV-2, there is the potential to enhance the compound libraries with additional novel compounds. To help address this need, IBM Research has recently created a new, AI-generative framework which can rapidly identify novel peptides, proteins, drug candidates and materials.
We have applied this AI technology against three COVID-19 targets to identify 3,000 new small molecules as potential COVID-19 therapeutic candidates. IBM is releasing these molecules under an open license, and researchers can study them via a new interactive molecular explorer tool to understand their characteristics and relationship to COVID-19 and identify candidates that might have desirable properties to be further pursued in drug development.
To streamline efforts to identify new treatments for COVID-19, we are also making the IBM Functional Genomics Platform available for free for the duration of the pandemic. Built to discover the molecular features in viral and bacterial genomes, this cloud-based repository and research tool includes genes, proteins and other molecular targets from sequenced viral and bacterial organisms in one place with connections pre-computed to help accelerate discovery of molecular targets required for drug design, test development and treatment.
Select IBM collaborators from government agencies, academic institutions and other organizations already use this platform for bacterial genomic study. And now, those working on COVID-19 can request the IBM Functional Genomics Platform interface to explore the genomic features of the virus. Access to the IBM Functional Genomics Platform will be prioritized for those conducting COVID-19 research. To learn more and request access, please click here.
Drug and Disease Information
Clinicians and healthcare professionals on the frontlines of care will also have free access to hundreds of pieces of evidence-based, curated COVID-19 and infectious disease content from IBM Micromedex and EBSCO DynaMed. Using these two rich decision support solutions, users will have access to drug and disease information in a single and comprehensive search. Clinicians can also provide patients with consumer-friendly patient education handouts with relevant, actionable medical information. IBM Micromedex is one of the largest online reference databases for medication information and is used by more than 4,500 hospitals and health systems worldwide. EBSCO DynaMed provides peer-reviewed clinical content, including systematic literature reviews in 28 specialties for comprehensive disease topics, health conditions and abnormal findings, to highly focused topics on evaluation, differential diagnosis and management.
The scientific community is working hard to make important new discoveries relevant to the treatment of COVID-19, and we’re hopeful that releasing these novel tools will help accelerate this global effort. This work also outlines our long-term vision for the future of accelerated discovery, where multi-disciplinary scientists and clinicians work together to rapidly and effectively create next generation therapeutics, aided by novel AI-powered technologies.
Grant will allow company to accelerate access to its AI solutions and use of ultrasound in COVID-19 emergency settings
TEL AVIV, Israel, May 12, 2020 /PRNewswire-PRWeb/ — DiA Imaging Analysis, a leading provider of AI based ultrasound analysis solutions, today announced that it has received a government grant from the Israel Innovation Authority (IIA) to develop solutions for ultrasound imaging analysis of COVID-19 patients using Artificial Intelligence (AI).Using ultrasound in point of care emergency settings has gained momentum since the outbreak of COVID-19 pandemic. In these settings, which include makeshift hospital COVID-19 departments and triage “tents,” portable ultrasound offers clinicians diagnostic decision support, with the added advantage of being easier to disinfect and eliminating the need to transport patients from one room to another.However, analyzing ultrasound images is a process that it is still mostly done visually, leading to a growing market need for automated solutions and decision support.As the leading provider of AI solutions for ultrasound analysis and backed by Connecticut Innovations, DiA makes ultrasound analysis smarter and accessible to both new and expert ultrasound users with various levels of experience. The company’s flagship LVivo Cardio Toolbox for AI-based cardiac ultrasound analysis enables clinicians to automatically generate objective clinical analysis, with increased accuracy and efficiency to support decisions about patient treatment and care.
The IIA grant provides a budget of millions NIS to increase access to DiA’s solutions for users in Israel and globally, and accelerate R&D with a focus on new AI solutions for COVID-19 patient management. DiA solutions are vendor-neutral and platform agnostic, as well as powered to run in low processing, mobile environments like handheld ultrasound.Recent data highlights the importance of looking at the heart during the progression of COVID-19, with one study citing 20% of patients hospitalized with COVID-19 showing signs of heart damage and increased mortality rates in those patients. DiA’s LVivo cardiac analysis solutions automatically generate objective, quantified cardiac ultrasound results to enable point-of-care clinicians to assess cardiac function on the spot, near patients’ bedside.
According to Dr. Ami Applebaum, the Chairman of the Board of the IIA, “The purpose of IIA’s call was to bring solutions to global markets for fighting COVID-19, with an emphasis on relevancy, fast time to market and collaborations promising continuity of the Israeli economy. DiA meets these requirements with AI innovation for ultrasound.”DiA has received several FDA/CE clearances and established distribution partnerships with industry leading companies including GE Healthcare, IBM Watson and Konica Minolta, currently serving thousands of end users worldwide.”We see growing use of ultrasound in point of care settings, and an urgent need for automated, objective solutions that provide decision support in real time,” said Hila Goldman-Aslan, CEO and Co-founder of DiA Imaging Analysis, “Our AI solutions meet this need by immediately helping clinicians on the frontlines to quickly and easily assess COVID-19 patients’ hearts to help guide care delivery.”
About DiA Imaging Analysis:
DiA Imaging Analysis provides advanced AI-based ultrasound analysis technology that makes ultrasound accessible to all. DiA’s automated tools deliver fast and accurate clinical indications to support the decision-making process and offer better patient care. DiA’s AI-based technology uses advanced pattern recognition and machine-learning algorithms to automatically imitate the way the human eye detects image borders and identifies motion. Using DiA’s tools provides automated and objective AI tools, helps reduce variability among users, and increases efficiency. It allows clinicians with various levels of experience to quickly and easily analyze ultrasound images.
The ubiquitin system produces a protein that greatly restricts the development of cancerous tumors.
A new study by researchers at the Technion-Israel Institute of Technology could hold one key to control cancer cell growth and development. In a paper published in the April 9, 2015 edition of CELL, the team reports on the discovery of two cancer-suppressing proteins.
Distinguished Professor Aaron Ciechanover. Photographer: Dan Porges
The research was conducted in the laboratory of Distinguished Professor Aaron Ciechanover, of the Technion Rappaport Faculty of Medicine. The team was led by research associate Dr. Yelena Kravtsova-Ivantsiv and , included additional research students and colleagues, as well as physicians from the Rambam, Carmel and Hadassah Medical Centers, who are studying tumors and their treatment.
The heretofore-undiscovered proteins were found during ongoing research on the ubiquitin system, an important and vital pathway in the life of the cell, which is responsible for the degradation of defective proteins that could damage the cell if not removed. The ubiquitin system tags these proteins and sends them for destruction in the cellular complex known as the proteasome. The system also removes functional and healthy proteins that are not needed anymore, thereby regulating the processes that these proteins control.
Usually, the proteins that reach the proteasome are completely broken down, but there are some exceptions, and the current line of research examined p105, a long precursor of a key regulator in the cell called NF-κB. It turns out that p105 can be broken down completely in certain cases following its tagging by ubiquitin, but in other cases it is only cut and shortened and becomes a protein called p50.
NF-κB has been identified as a link between inflammation and cancer. The hypothesis of the connection between inflammatory processes and cancer was first suggested in 1863 by German pathologist Rudolph Virchow, and has been confirmed over the years in a long series of studies. Ever since the discovery (nearly 30 years ago) of NF-κB, numerous articles have been published linking it to malignant transformation. It is involved in tumors of various organs (prostate, breast, lung, head and neck, large intestine, brain, etc.) in several parallel ways, including: inhibition of apoptosis (programmed cell death) normally eliminates transformed cells; acceleration of uncontrolled division of cancer cells; formation of new blood vessels (angiogenesis), which are vital to tumor growth; and increased resistance of cancerous cells to irradiation and chemotherapy.
The dramatic effect of these proteins on cancer growth: above the two tumors in the foreground (the control group) are tumors that express high levels of the proteins
As noted, the precursor p105 is “handled” by the ubiquitin system in one of two parallel and equally prevalent ways. It is either destroyed completely, or shortened and transformed to p50. The current research deciphers the decision-making mechanism that determines which process will be applied to the protein: when a ubiquitin system component called KPC1 is involved in the process and attaches ubiquitin to p105, the protein is shortened to become p50. When ubiquitination is mediated by another component of the system (and without KPC1), p105 is degraded.
The ubiquitin molecule within all living cells
The decision between these two options has significant implications on the cell, as the presence of high levels of KPC1 (which generates p50) and p50 (the product of the process) – with the accompanying disruption of the normal ratios between the processes – suppresses the malignant growth and apparently protects the healthy tissue. The current research was conducted on models of human tumors grown in mice, as well as on samples of human tumors, and a strong connection was discovered between the suppression of malignancy and the level of the two proteins, clearly indicating that the increased presence of KPC1 and/or p50 in the tissue can protect it from cancerous tumors.
Professor Ciechanover, who is also the president of the Israel Cancer Society, notes that many more years are required “to establish the research and gain a solid understanding of the mechanisms behind the suppression of the tumors. The development of a drug based on this discovery is a possibility, although not a certainty, and the road to such a drug is long and far from simple.”
Professor Ciechanover won the Nobel Prize in Chemistry in 2004 (jointly with Professors Avram Hershko – also from the Technion – and Irwin Rose, of the Fox Chase Cancer Center) for the discovery of the ubiquitin system. The current line of research is a continuation of that discovery.
President Reuven Rivlin and Indian Prime Minister Narendra Modi, March 29, 2015 (photo credit: Courtesty Tomer Reichmann)
President Reuven Rivlin and Indian Prime Minister Narendra Modi, March 29, 2015 (photo credit: Courtesty Tomer Reichmann)
Days after the Technion announced that a team led by Nobel Prize laureate Professor Aaron Ciechanover had discovered how proteins could be used to suppress cancer and control tumor growth and development, the institute revealed that it had entered into an exclusive agreement with India’s Sun Pharmaceuticals — the world’s fifth-largest specialty generic pharmaceutical company and India’s top pharmaceutical company.
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Under the agreement, researchers from the Technion and Sun will conduct studies on how high concentrations of two proteins can protect tissue from tumors. A study published in the medical journal Cell this week discussed how the proteins can suppress malignancies.
Along with Ciechanover, the research team included Dr. Gila Maor and Professor Ofer Binah. In a statement, Ciechanover said that the research held a great deal of promise of an effective drug for treating cancer, “although this is not a certainty, and the road to such a drug is long and far from simple.”
The deal with Sun is just one of several R&D ventures between Israel and India, on both the business and government levels. So far, the two countries have signed seven bilateral economic and R&D agreements, including one that fosters joint projects on space travel and satellite development.
The joint program aims at attracting additional, world-class support from institutions and individuals who are dedicated to eradicating cancer through focused and efficient research.
Two of the world’s preeminent academic and research institutions — New York University’s Langone Medical Center and Haifa’sTechnion-Israel Institute of Technology — have made a “groundbreaking step forward to advance global collaboration in the fight against cancer formally.
On Wednesday night, they announced a $9 million gift from philanthropists Laura and Isaac Perlmutter that will fund two major, joint research endeavors with potentially far-reaching impact in advancing cancer research. The joint program aims at attracting additional, world-class support from institutions and individuals who are dedicated to eradicating cancer through focused and efficient research, they said in a joint statement.
The first $3 million of the grant will finance six cancer-focused research projects to be conducted by teams spearheaded by co-investigators from both NYU and the Technion. The remaining $6 million will be used to establish a state-of-the-art research facility on Technion’s campus that will support these and other research projects and focus mainly on the emerging field of cancer metabolomics.
“NYU Langone and the Technion have a shared, longstanding commitment to advancing cancer research,” said Dr. Dafna Bar-Sagi, senior vice president and vice dean for science at the New York hospital, chief science officer at NYU School of Medicine and a principal architect of the NYU Langone-Technion partnership. “We are now at a great moment in our institutions’ illustrious histories, a point from which we can jointly leverage the talent and creativity of our researchers toward accelerating breakthroughs. The foresight and the generosity of the Perlmutters, particularly at this time of financial challenge in funding for basic research, will have tremendous impact.”
“Bringing together the unique expertise of researchers from both NYU and the Technion will hopefully enable us to overcome some of the most difficult challenges in treating cancer patients,” said Technion Prof. Aaron Ciechanover, the 2004 Nobel Prize Laureate in Chemistry and Distinguished Research Professor and head of the David and Janet Polak Cancer and Vascular Biology Research Center at the Technion Faculty of Medicine.
Renowned cancer biologist Dr. Benjamin Neel, an expert in the field of cell signal transduction, recently joined the Langone faculty as director of the Perlmutter Cancer Center, and Dr. Eyal Gottlieb, a world leader in cancer metabolism, has been recruited to lead the new research facility at the Technion funded by the Perlmutter gift. Neel will work closely with Ciechanover to lead the collaborative cancer research effort between the two institutions, they said.
In addition, Neel will oversee at NYU the building of world-class translational programs in immunotherapy, cancer genetics/targeted therapies and epigenetics, imaging, as well as expanded programs in clinical care, community outreach and supportive oncology.
The innovative method, developed at the Technion, identifies persons at risk for developing stomach cancer and for detecting tumors at an earlier stage. The prestigious journal Gut, which published the research, notes that the detection method is quick, simple, inexpensive and non-invasive.
Innovative gastric cancer-detection technology
Innovative gastric cancer-detection technology developed by the Technion can be used for the early detection of stomach cancer and for identifying persons at risk for developing the disease. The new detection method, based on breath analysis, has significant advantages over the existing detection technology: Gut reports that the new method is quick, simple, inexpensive and non-invasive.
Gastric cancer is one of the most lethal forms of cancer and in most cases, its diagnosis involves an endoscopy (the insertion of a tube into the esophagus, requiring that the patient fast and receive an intravenous sedative). Treatment is aggressive chemotherapy, radiation and the full or partial removal of the stomach. The disease develops in a series of well-defined steps, but there’s currently no effective, reliable, and non-invasive screening test for picking up these changes early on. Thus, many people succumb to stomach cancer only because it was not diagnosed in time.
The new technology, developed by Prof. Hossam Haick of the Wolfson Faculty of Chemical Engineering, can be used to detect premalignant lesions at the earliest stage, when healthy cells start becoming cancerous.
The research, published in Gut as part of the doctoral thesis of Mr. Haitham Amal, was conducted in conjunction with a Latvian research group headed by Prof. Marcis Leja, based on the largest population sample ever in a trial of this type. 484 people participated in the trial, 99 of whom had already been diagnosed with stomach cancer. All the participants were tested for Helicobacter pylori, a bacterium known to increase the risk for stomach cancer, and two breath samples were taken from each person.
The first sample from each participant was analyzed using the GCMS technique, which measures volatile organic substances in exhaled breath. The researchers noted that GCMS technology cannot be used to detect stomach cancer because the testing is very expensive and requires lengthy processing times and considerable expertise to operate the equipment.
The second breath sample was tested using nanoarray analysis, the unique technology developed by Prof. Haick, combined with a pattern recognition algorithm.
The findings:
Based on the concentrations of 8 specific substances (out of 130) in the oral cavity, the new technology can distinguish between three groups: gastric cancer patients, persons who have precancerous stomach lesions, and healthy individuals.
The new technology accurately distinguishes between the various pre-malignant stages.
The new technology can be used to identify persons at risk for developing gastric cancer.
The diagnosis is accurate, regardless of other factors such as age, sex, smoking habits, alcohol consumption and the use of anti-oxidant drugs.
In short, the nano-array analysis method developed by Prof. Haick is accurate, sensitive technology that provides a simple and inexpensive alternative to existing tests (such as GCMS). This new technology offers early, effective detection of persons at risk for developing stomach cancer, without unnecessary invasive tests (endoscopy). In order to assess the accuracy and effectiveness of the new, a wide-scale clinical trial is currently under way in Europe, with thousands of participants who have cancerous or pre-cancerous tumors.
About Prof. Hossam Haick
Prof. Hossam Haick, who joined the senior staff at the Technion Wolfson Faculty of Chemical Engineering in 2006, has been working since that year on the development of innovative, non-invasive technology for detecting cancer and other diseases. This technology is based on an “electronic nose” – an apparatus capable of detecting illnesses by analyzing a patient’s exhaled breath.
Prof. Haick, a native of Nazareth, completed his Ph.D. studies at the Technion by the time he was 27 and went to the Weizmann Institute of Science in Rehovot and Caltech Institute of Technology in California. He returned to the Technion in 2006 and his research group was awarded one million euros in grants by the European Union, which was very impressed by his research into artificial olfactory systems. Today he heads a consortium that includes Siemens and several universities, research institutes and companies in Germany, Austria, Finland, Ireland, Latvia and Israel. Since joining the senior faculty in the Chemical Engineering Department in 2006, Prof. Haick has won dozens of awards, grants and international honors. These include the Marie Curie Excellence Grant, European Research Council (ERC) grant and the Bill & Melinda Gates Award. Prof. Haick was nominated to MIT’s list of the 35 leading young scientists worldwide, received the Knight of the Order of Academic Palms, from the French Government and won the Hershel Rich Technion Innovation Award (twice), as well as the Tenne Prize for Excellence in the Science of Nanotechnology. He has also been recognized for his outstanding teaching skills and is the recipient of the Yanai Prize for Academic Excellence. In 2014, at the initiative of the president of the Technion, Prof. Haick headed an MOOC (Massive Open Online Course) in nanotechnology and nano-sensors that had an enrollment of 42,000.
This month is Breast Cancer Awareness Month in Israel and around the world. Innovative technology developed at the Technion Faculty of Biomedical Engineering will enable the prediction of cancer metastasis after the appearance of breast cancer. The technology, whose efficacy has been proven in preliminary laboratory-trials, is entering into advanced testing using cells from patients undergoing surgery.
In contrast to benign cells (right), metastatic cells (left) penetrate into the gel and disappear inside it, thanks to their unique characteristics
Assistant Professor Daphne Weihs recently achieved a research breakthrough: the unique technology that she developed – a biomechanical method for early detection of metastatic cancer – was approved by the Ethics Committee. This means that the technology that was found to be effective in tests on cell lines will advance to trials with tumor cells collected directly after surgery, in cooperation with Rambam Healthcare Campus.
According to Assistant Professor Weihs, the practical concept is that “during or immediately after a biopsy or surgery on a malignant tumor, the system will enable the medical team to quantitatively evaluate the likelihood of the presence or development of tumor metastases in other organs, and to propose which organ or organs are involved. Such knowledge will make it possible to act at a very early stage to identify and curb these metastases and, moreover, to prevent the primary tumor from metastasizing further.
Cancer is a general name for a wide family of diseases – more than 200 – whose common denominator is that the cell division rate becomes uncontrolled and the cells become immortal. In other words, the cancer mechanism disrupts the normal cell division process and converts it into “wild” and rapid division. Since the cells do not age and do not die, the original, primary tumor expands, invades and takes over more and more nearby tissue. In addition, apart from spreading to its immediate vicinity, a tumor that has become very aggressive “knows” how to send metastases to more distant tissues through the lymph and circulatory systems. Metastases (secondary tumors) are usually more dangerous than the primary tumor because it is difficult to identify them at their inception. When they are detected at an advanced stage, treating them medically is more complicated and the medical prognosis is typically not good.
“In fact, most cancer-related deaths are caused by metastases rather than by the primary tumor, and therefore vast resources are invested in developing methods for early detection of metastases,” explains Assistant Professor Daphne Weihs. “Early detection means timely and more effective treatment. The new approach that we are developing will enable early prediction of the likelihood of the formation of metastases and where in the body their development is probable. This prediction is based on identifying the biomechanics of the primary tumor cells, and does not require us to know the specific genetic makeup of the tumor.”
Diagnostic system developed by Technion professor is to pair with tiny smell-sensitive sensor that can go anywhere
By David Shamah February 3, 2015, 2:05 pm
A patient uses the NaNose breathalyzer (Photo credit: Courtesy Technion)
Writers
David Shamah
An innovative early disease detection system that uses the sense of smell is going mobile.
The NaNose breathalyzer technology developed by Professor Hossam Haick of the Technion will soon be installed in a mobile phone – to be called, appropriately, the SniffPhone. A tiny smell-sensitive sensor will be installed onto a phone add-on, and using specially designed software, the phone will be able to “smell” users’ breath to determine if they have cancer, among other serious diseases.
By identifying the special “odor” emitted by cancer cells, the NaNose system can detect the presence of tumors, both benign and malignant, more quickly, efficiently and cheaply than previously possible, said Haick.
“Current cancer diagnosis techniques are ineffective and impractical,” he said. NaNose technology, he said, “could facilitate faster therapeutic intervention, replacing expensive and time-consuming clinical follow-up that would eventually lead to the same intervention.”
According to research done by Haick’s team, the NaNose system has a 90 percent accuracy rate.
The smartphone device is just a vehicle to implement the NaNose technology that can be taken anywhere and used in any circumstances, including in rural areas of the developing world where bringing in sophisticated testing equipment is impossible.
The plan calls for a chip with NaNose technology to be installed in a device that is attached to a smartphone, and for an app to read the sensor data, analyzing it on the device or uploading it to the cloud for processing.
NaNose technology will be especially useful in battling lung cancer, said Haick. According to US government statistics, lung cancer kills more Americans annually than the next three most common cancers — colon, breast, and pancreatic — combined. The reason, doctors say, is because lung cancer is so difficult to detect. Currently, the only way to detect early-stage lung cancer is through an extensive process involving blood tests, biopsies, CT scans, ultrasound tests, and other procedures — and even then, detection is difficult.
“Mostly the patient arrives for diagnosis when the symptoms of the sickness have already begun to appear,” said Haick, describing the drawbacks in current detection protocols. “Months pass before a real analysis in completed. And the process requires complicated and expensive equipment such as CT and mammography imaging devices. Each machine costs millions of dollars, and ends up delivering rough, inaccurate results.”
Dr. Hossam Haick (Photo credit: Courtesy)
The NaNose-based system, on the other hand, doesn’t require anything more than a patient’s breathing into the device in order to come up with an initial diagnosis. Lung cancer tumors produce chemicals called volatile organic compounds (VOCs), which easily evaporate into the air and produce a discernible scent profile. Haick’s NaNose chip detects the unique “signature” of VOCs in exhaled breath. In four out of five cases, the device differentiated between benign and malignant lung lesions and even different cancer subtypes.
The project is being funded by the European Commission, which has given the consortium developing it a six million euro grant. The developers include universities and research institutes from Germany, Austria, Finland, Ireland and Latvia, as well as Irish cell biology research firm Cellix, with the NaNose system the centerpiece of the technology. That Israeli-developed component will be delivered by an Israeli start-up called NanoVation-GS, a spinoff of the Technion. Professor Haick serves as the start-up’s Chief Science Officer.
“The SniffPhone is a winning solution. It will be made tinier and cheaper than disease detection solutions currently, consume little power, and most importantly, it will enable immediate and early diagnosis that is both accurate and non-invasive,” said Haick. “Early diagnosis can save lives, particularly in life-threatening diseases such as cancer.”
Anyone who knows a person in the midst of chemotherapy is aware that anti-cancer drugs often take a very harsh toll on the body. This is one reason scientists have been trying to develop improved means of drug delivery for years. Now, a Technion research team discovered a way to improve drug delivery to tumors using Nanostructured Porous Silicon (PSi) particles (instead of an IV drip), a method that’s emerging as a promising new platform for drug delivery. In the future, PSi could be used in cancer treatments, potentially offering an alternative to traditional chemotherapy, which is notorious for its agonizing side effects.
The silicon “carriers” used in this study to deliver chemotherapy drugs behave differently in cancerous tumors than they do in healthy tissues. Therefore, the findings could help scientists to design nano-carriers that deliver drugs to tumors, instead of treating patients with traditional, intravenous chemotherapy. However, it would take years to develop and apply this new type of drug delivery method, which would potentially be taken orally.
So far, these nano-silicon “containers” have been studied in vitro – outside of a living organism – rather than in an environment that behaves more closely to that of a tumor in a cancer patient’s body. The Technion research team looked at what happens to PSi particles when they’re injected into the area around the tumor in mice. The significant differences in the area around a cancerous growth and regular healthy tissue have been widely described and studied; however, the effect on these porous silicon “containers,” or carriers, was unknown until now.
Prof. Ester Segal of the Technion – Israel Institute of Technology, who led this joint study with the Massachusetts Institute of Technology (MIT) and the Harvard Medical School, said the team has “shown for the first time that bio-materials in general, and Nanostructured Porous Silicon in particular, behave differently when they are injected (or implanted) at the tumor micro-environment.”
Revolutionizing cancer treatments
Silicon materials could revolutionize treatments in a way that no existing drug delivery does. Prof. Segal tells NoCamels that the silicon containers “could deliver drugs over a long period of time – weeks or even months”, something no existing chemotherapeutic delivery mechanism can do currently.
Cancer cells
The special properties of these porous nano-silicon carriers lie in their large surface area, which can ferry many or large drug molecules. Additionally, due to their biodegradability they’re able to break down into harmless silicic acid, which is expelled through urination. They are also biocompatible, so they do not stimulate any inflammation or clotting. Another benefit to these nano-silicon containers is their versatility. They can be ingested, injected or implanted, and they can be designed to carry a wide range of dosage sizes. In the process of their study, lab members also developed an approach to determining how biomaterials will react in settings more similar to their eventual clinical purpose – treating cancer, for example.
In a separate study, Tel Aviv University scientists recently founda strategy that would stop brain tumor cell proliferation with similar nano-particles. “It is a basic, elegant mechanism and much less toxic than chemotherapy,” TAU’s Prof. Dan Peer said in a statement.
These works underline the importance of such studies in successfully developing bio-delivery materials that will have therapeutic benefits in the near future.
“Nano-skeletons’ (in red) delivered to human tissue infected by prostate cancer. The infected cells are colored in blue (PIP) and green (cytoplasmic); it is possible to see how the ‘nano-skeletons’ reach them
Florida native Dr. Beth Schoen, is part of a team developing a novel platform for delivering anti-cancerous drugs directly to its mark as part of her postdoctoral research at the Technion
Beth Schoen, born in Hollywood Florida, came to the Technion to conduct her postdoctoral research at age 26. In her very limited spare time she plays soccer for the leading all women’s soccer team – Maccabi Hadera – and studies Hebrew. “The Hebrew thing is no simple matter,” she confesses, “but I’m willing to make the effort, because it’s clear to me that Israel is where I want to live.”
Dr. Beth Schoen completed her undergraduate degree at the University of Florida, and her doctorate at Michigan State University in chemical engineering. “My doctoral studies focused on synthetic organic chemistry, particularly on the development of polymers with unique thermodynamic attributes especially resistant to high temperatures. These types of materials are used in part for the production of jet engine parts, body armor and Nomex (used for making fire-resistant gloves and overalls). One of our tasks was to create soft sheets that were not brittle, to be worn to be both bulletproof and fire resistant. It was a theoretical study, but as part of the process I also produced some of these polymers and tested them.”
Dr. Schoen planned to come to the Technion as part of her doctoral studies, but, she adds, “It didn’t work out, so I started to check where I could best fit in here in my future studies.” She decided to join Prof. Marcelle Machluf’s laboratory, at the Faculty of Biotechnology and Food Engineering, “I was eager to move from chemistry to biology and pursue cancer research in particular. I was very glad for the tremendous opportunity that Marcelle gave me in taking me on – perhaps it was because of my experience in nanomaterials and polymers.”
Prof. Marcelle Machluf’s research team consists of 17 female and 3 males students, researchers and technicians working on two main projects: (1) the development of scaffolds to rehabilitate damaged heart-tissue, and (2) the development of new technology to deliver drug treatment to damaged (sick) tissue (specifically related to cancer therapy). In an interview with her she focused on the second project.
“The current treatment for cancer involves radiotherapy and chemotherapy usually administered through intravenous infusion. The cancer drugs available are extremely effective, yet the way they are put to use in present day treatment, they also cause damage to healthy tissues. These are very potent drugs – they are intended to kill cancer cells – and on their way they also end up killing healthy ones.”
“The greatest damage is caused to rapidly dividing cells, which are similar to cancer cells. Hair follicle cells, for example, are a type of rapidly dividing cells and they damage easily from these types of treatment, which explains the hair loss in patients undergoing chemotherapy. Other side-effects include nausea and hearing loss, sometimes even leading to deafness. The drug Cisplatin for example, is a type of chemo drug used to treat various types of lung and breast cancers; some of its side-effects include damage to renal and immune system functioning, putting patients at risk to infections and diseases.”
These impediments are what fuel Prof. Machluf’s drive to develop a new drug delivery platforms capable of delivering anti-cancer drugs directly to the tumor without damaging healthy tissues on its way. “This is the top priority of cancer treatment: to develop a ‘magic bullet’ that target cancer cells,” explains Prof. Machluf. “And our new platform may be the solution to this great challenge.”
The new platform is based on ‘depleting’ specific cells – mesenchymal stem cells – so that there is nothing left of them save for the membrane. This membrane, called a ghost cells can be down sized to nano-vesicles, termed nano-ghosts, which can be loaded with any drug and delivered by injection directly into the blood stream. The immune system falls for the trap and does not recognize the ‘intruder,’ instead it treats these cells as if they were naturally part of the system and sends them to the afflicted area. On the way to their target they do not release the drug they are carrying and therefore do not do any damage to healthy tissues. Only upon reaching the malignant tissue, which they know how to identify, do they break down and secrete their contents at the site of the tumor cells.
This original idea was tested in a long series of experiments, and the results are very impressive: these nano-ghosts are in fact tumor selective, no matter the type of tumor. They ‘dash’ straight to the malignant tissue without emitting their drug on the way and without damaging healthy cells. Moreover, this unique ‘parcel’ increases the effectiveness of the treatment by ten-fold. Animal studies have shown that the employment of nano-ghosts for anti-cancer drug delivery have led to an 80% delay of prostate cancer – an unprecedented rate.
Still, there is a lot of work ahead, as Prof. Machluf’s research team works on improving the mechanism of this novel new platform: some of them are focusing on compatibility with specific drugs while others, like Dr. Beth Schoen, are concentrating on improving the nano-ghosts “This platform must be very precise,” explains Schoen. “It must be able to endure travelling through the entire human body, and release its contents only inside the tumor.”
Groundbreaking for the future campus will begin early next year on Roosevelt Island, a quiet, residential two-mile strip of land between Manhattan and Queens in the East River. As part of Mayor Bloomberg’s 2011 initiative, Cornell Tech was awarded a 99-year lease to the 12.5-acre site along with $100 million in city capital for site maintenance and construction. Cornell’s plans to build and develop the campus include demolition of the island’s Coler-Goldwater Specialty Hospital & Nursing Facility. The new campus will include up to 2.1 million square feet of development and will house approximately 2,000 students and 280 faculty members by 2037.
Cornell NYC Tech by the numbers; click to enlarge (Source: nyc.gov)
Dan Huttenlocher, Dean and Vice Provost of Cornell Tech, told MetroFocus host Rafael Pi Roman the most challenging part of the process has been “…getting the culture right. We’re building a new organization. That organization is really intended to be a model for the world, to bring together academic excellence and academic leadership with real world impact.”
Cornell chose the Technion-Israel Institute of Technology in Haifa as its international partner. Craig Gotsman, Founding Director of theJoan and Irwin Jacobs Technion-Cornell Innovation Institute, told Pi Roman, “one of the reasons the Technion is involved in the first place, is that the innovation and the entrepreneurship that you see in Israel is something that the city of New York wants to have here in New York City.” The New York Times reports that Technion graduates in high-tech industries have an annual estimated output of at least $21 billion. While the partnership has been at times controversial, The Cornell Daily Sun reports that Cornell Provost Kent Fuchs has said the partnership “is intended not as a political statement, but rather as an opportunity for the University to foster global academic cooperation.”
We’re building a new organization. That organization is really intended to be a model for the world, to bring together academic excellence and academic leadership with real world impact.
—Dan Huttenlocher
The City of New York will act as a “third partner” in the campus by connecting students and faculty directly to businesses in the city’s growing tech sector. In recent years, the city has risen as a success story in the tech community. According to The Center for an Urban Future‘s recent report “New Tech City,” the number of information technology jobs in the city climbed 60% in less than ten years – from 33,000 in 2003 to 52,900 in 2012. “New Tech City” also reported that the number of venture capital deals in New York rose by 32% in that period, while it fell by about 11% across the nation. Today, Mayor Bloomberg’s economic development initiative, “We Are Made in New York,” reports that over 1,000 city tech companies are currently hiring.
The plans for Cornell Tech have prompted debates about whether New York’s “Silicon Alley” will become a force to rival California’s Silicon Valley. When asked whether Cornell [NYC] Tech will help the city surpass Silicon Valley’s tech economy, Huttenlocher noted that it’s more about identifying and harnessing the city’s strengths to set New York apart from other high-tech sectors around the world. “We’re the center of so many of these information-rich industries, bringing real technology expertise here, on the ground, in New York City, we think is a unique opportunity for New York to lead in the next century of information technology development,” said Huttenlocher.
To watch Prof. Lander’s talk on “Secrets of The Human Genome/Biology,” click here.
To watch Prof. Lander’s talk on “Secrets of the Human Genome/Medicine,” click here.
To watch Prof. Yablonovitch’s talk, entitled “Photonic Crystals in Science, Engineering and the World of Nature, click here.
Biology Professor Eric S. Lander of the Eli and Edythe Broad Institute of the Massachusetts Institute of Technology and Harvard University, and Eli Yablonovitch, Professor of Electrical Engineering and Computer Science at the University of California, Berkeley, were awarded the 2012 Harvey Prize in a ceremony April 30 at the Technion-Israel Institute of Technology in Haifa, Israel.
The awarding of the Harvey Prize is watched closely worldwide, as it is often regarded as a strong predictor of future Nobel Prize laureates. The international prize is awarded annually by the Technion in a variety of disciplines within the categories of Science and Technology and Human Health. It has also been awarded for contributions to Peace in the Middle East.
Prof. Lander, the founding director of the Broad Institute and one of the principal leaders of the Human Genome Project, received the award in the area of Human Health for his contributions to the field of genomics. Calling Prof. Lander a “driving force behind most of the major advances in this field,” the citation for the prize read: “He has made important contributions by both developing methods to exploit the power of genetic information and leading large endeavors to identify and annotate entire genomes. Most notably, he consolidated the efforts of the Human Genome Project and first authored the resulting historic manuscript. Prof. Lander also pioneered the analysis of the genetic components underlying complex diseases, including cancer.”
Prof. Eric Lander speaks during the Harvey Prize Ceremony.
Also pictured is Technion Prof. Eliezer Shalev
In accepting his award, Prof. Lander credited his success to a series of “lucky accidents,” including a chance meeting with Princeton University Professor David Botstein, who invited Prof. Lander to work with him on mapping diseases. “I had no inkling of what was yet to come. But the idea of the Human Genome Project was in the air.” He recounted an unlikely career, in which he studied mathematics and taught business before discovering the sense of “shared purpose” in working collaboratively on a larger project.
Prof. Lander, who is the Professor of Biology at MIT and Professor of Systems Biology at Harvard Medical School, has received numerous awards including the MacArthur Foundation Fellowship, the Gairdner Foundation International Award, the Max Delbruck Medal, the American Association for the Advancement of Science’s Award for Public Understanding of Science and Technology, among others, and eight honorary doctorates. In 2009, President Obama appointed him to co-chair the President’s Council of Advisors on Science and Technology.
Prof. Yablonovitch, the Director of the National Science Foundation Center for Energy Efficient Electronics Science at UC Berkeley, received the award in the area of Science and Technology in recognition of “his pioneering discoveries in the fields of photonics, optoelectronics and semiconductors.” In his photovoltaic research, Prof. Yablonovitch introduced the 4n2 light-trapping factor that is in worldwide use for almost all commercial solar panels. This factor, sometimes called the “Yablonovitch Limit” increased the theoretical limits and practical efficiency of solar cells. Prof. Yablonovitch is also regarded as the Father of the Photonic BandGap concept, and as having coined the term “Photonic Crystal.”
Prof. Eli Yablonovitch
In accepting his award Prof. Yablonovitch, who holds the James & Katherine Lau Chair in Engineering, credited Israel for its success in educating young scientists. But he noted that Israel should provide job opportunities for “graduates to further develop their scientific potential” post-graduate school, as he was able to do at Bell Laboratories.
Prof. Yablonovitch has received numerous awards including the Institute of Electrical and Electronics Engineers’ (IEEE) Photonics Award, The Institution of Engineering and Technology’s Mountbatten Medal, the Julius Springer Prize, the R.W. Wood Prize, the W. Streifer Scientific Achievement Award, and the Adolf Lomb Medal. He holds two honorary doctorates, is a Fellow of the IEEE, and a member of both the National Academy of Sciences and the American Academy of Arts & Sciences.
The Harvey Prize was first awarded in 1972 from a fund established by the late Leo M. Harvey, and maintained by his son, Technion Guardian Homer Harvey and the Harvey Family of Los Angeles. Some 13 Harvey Prize recipients have also been awarded the Nobel Prize including former Soviet Union leader Mikhail Gorbachev, and Israelis Robert Aumann and Ada Yonath.
Below please find links to films from the event, including the musical performances from the ceremony, acceptance speeches and academic lectures.
To watch the ceremony speech given by Prof. Lander, click here.
To watch the ceremony speech given by Prof. Yablonovitch, click here.
To watch Prof. Lander’s talk on “Secrets of The Human Genome/Biology,” clickhere. To see his talk on “Secrets of the Human Genome/Medicine,” click here.
To watch Prof. Yablonovitch’s talk, entitled “Photonic Crystals in Science, Engineering and the World of Nature, click here.
The Technion-Israel Institute of Technology is a major source of the innovation and brainpower that drives the Israeli economy, and a key to Israel’s renown as the world’s “Start-Up Nation.” Its three Nobel Prize winners exemplify academic excellence. Technion people, ideas and inventions make immeasurable contributions to the world including life-saving medicine, sustainable energy, computer science, water conservation and nanotechnology. The Joan and Irwin Jacobs Technion-Cornell Innovation Institute is a vital component of Cornell NYC Tech, and a model for graduate applied science education that is expected to transform New York City’s economy.
American Technion Society (ATS) donors provide critical support for the Technion—more than $1.9 billion since its inception in 1940. Based in New York City, the ATS and its network of chapters across the U.S. provide funds for scholarships, fellowships, faculty recruitment and chairs, research, buildings, laboratories, classrooms and dormitories, and more.
Dr. Irwin Jacobs, Co-Founder, Chairman and CEO Emeritus of Qualcomm, was honored on May 20 with the Technion Medal, the greatest recognition by the Technion-Israel Institute of Technology, awarded only every three to five years. He received the medal during a festive event in Haifa, marking 20 years of Qualcomm activities in Israel.
Technion President Professor Peretz Lavie spoke about the long-standing friendship with the Technion and generous philanthropic activities of Dr. Jacobs and his wife Joan. The Technion’s Graduate School is named for them, as is the Center for Communications and Information Technologies (CCIT). Those gifts have supported Technion graduate students — arguably the engine behind any successful university— and have helped the CCIT promote cooperation and information flow between academia and industry. Recently, they made a $133 million gift to name the Joan and Irwin Jacobs Technion-Cornell Innovation Institute (JTCII), a key component of the new applied science campus in New York.
(From left) Technion President Peretz Lavie, and Joan and Irwin Jacobs
President Lavie expressed his appreciation to Dr. Jacobs: “Thank you so very much for all you have done for the Technion, engineering, the field of telecom, academia, Israel, and future scientists. You are truly a great leader, model citizen, and a real ‘mensch.’”
Dr. Jacobs returned the gratitude, saying it is not the Technion that needs to thank him, but rather he who needs to thank the Technion. “Many of Qualcomm’s employees are Technion graduates,” he said. “The company would not have attained many of its achievements if it hadn’t been for its brilliant employees.”
In 1993, Dr. Jacobs directed the then still young, San Diego-based digital wireless telecommunications company to launch Qualcomm Israel in Haifa to take advantage of Technion brainpower (the Mt. Carmel campus is about a 15-minute drive). Since then, Qualcomm Israel has become a key source of high-tech innovation in Israel, moving into such creative ventures as “Tagg,” a device that allows pet owners to track their pet’s location and activity level. Qualcomm’s recent investments in Israeli start-ups rival similar activities in all of Europe.
The Technion Medal was established in 1996 to award “exceptional individuals who have made unstinting efforts to advance humanity; … contribute to the welfare of the Jewish people and the State of Israel; and … strengthen the industrial, scientific and economic infrastructure of Israel.” Irwin Jacobs joins a short list of just 12 other Technion Medal recipients that includes Israel Supreme Court Justice Moshe Landau and Israeli war hero Gen. (Res.) Amos Horev — both former Technion Presidents; Technion graduate Uzia Galil, one of the founders of Israel’s high-tech industry, and the late Henry Taub, who held almost every honor and position within the American Technion Society (ATS), including national President and Chair of the Technion International Board of Governors for 13 years.
Dr. Jacobs earned his bachelor’s degree in electrical engineering from Cornell University and his master’s and doctorate degrees in electrical engineering and computer science from the Massachusetts Institute of Technology (MIT). He taught at both MIT and at University of California, San Diego, co-authored an engineering textbook and co-founded Linkabit Corporation, before helping start Qualcomm. The Technion recognized Dr. Jacobs with an honorary doctorate in 2000, and in 1996, the American Technion Society (ATS) granted him its highest honor, the Albert Einstein Award. He and his wife are Technion Guardians — a designation reserved for those who have reached the highest level of support.
The Technion-Israel Institute of Technology is a major source of the innovation and brainpower that drives the Israeli economy, and a key to Israel’s renown as the world’s “Start-Up Nation.” Its three Nobel Prize winners exemplify academic excellence. Technion people, ideas and inventions make immeasurable contributions to the world including life-saving medicine, sustainable energy, computer science, water conservation and nanotechnology. The Joan and Irwin Jacobs Technion-Cornell Innovation Institute is a vital component of Cornell NYC Tech, and a model for graduate applied science education that is expected to transform New York City’s economy.
American Technion Society (ATS) donors provide critical support for the Technion—more than $1.9 billion since its inception in 1940. Based in New York City, the ATS and its network of chapters across the U.S. provide funds for scholarships, fellowships, faculty recruitment and chairs, research, buildings, laboratories, classrooms and dormitories, and more.
Mayor Bloomberg Officially Transfers 12 Acres of Roosevelt Island to “Cornell Tech” – Technion-Cornell’s Jacobs Technion-Cornell Innovation Institute (JTCII)
Mayor Bloomberg, Cornell University President David J. Skorton, and Technion-Israel Institute of Technology President Peretz Lavie today formally executed a 99-year lease between the City of New York and Cornell Tech, which will pave the way for construction of the Cornell Tech campus on Roosevelt Island, exactly two years after Cornell and academic partner Technion were named the first winners of the City’sApplied Sciences NYC competition.
Cornell Tech is a revolutionary model for graduate-level technology education and is establishing itself as a world-leading institution, conferring graduate degrees and conducting research that drives technology, innovation, commercialization and the creation and retention of businesses and jobs in New York City. The land transfer will allow for groundbreaking on the campus to begin in January, with the first classrooms on Roosevelt Island set to open in 2017. Cornell Tech students began classes this fall in space donated by Google at their Chelsea headquarters on Eighth Avenue. Construction of the entire 2 million square foot build-out, which will span 12 acres on Roosevelt Island and house approximately 2,000 students and nearly 280 faculty and researchers, will be completed by 2043.
New details and renderings for the first phase of the full campus were also released today, revealing how the physical campus will be designed to support Cornell Tech’s focus on innovation, entrepreneurship and collaboration between academia and industry. Mayor Bloomberg and President Skorton signed the lease documents at a City Hall ceremony to finalize the official land transfer to Cornell Tech, where they were joined by President Lavie, Deputy Mayor for Economic Development Robert K. Steel, New York City Economic Development Corporation President Kyle Kimball, U.S. Representative Carolyn Maloney, Council Member and Borough President-Elect Gale Brewer, Council Member Jessica Lappin, Cornell Tech Vice President Cathy Dove, Cornell Board Chair Robert Harrison, Cornell Provost Kent Fuchs, Cornell Tech Dean Daniel Hutenlocher, Forest City Ratner Companies President and CEO MaryAnne Gilmartin, and Hudson Companies Principal David Kramer.
“Our goal has been to make New York City the global capital of technological innovation, and this new campus on Roosevelt Island is a central part of our strategy for achieving it,” said Mayor Michael R. Bloomberg. “It is one of the most ambitious and forward-looking economic development projects any city has ever undertaken, and it’s going to help add thousands of new jobs to our economy in the decades ahead.”
“The State was proud to work closely with the Mayor’s Office, RIOC and Cornell because we strongly believe that the path to New York State’s continued economic growth will largely be defined by partnerships that start with our State’s academic institutions,” said Governor Andrew M. Cuomo. “This project leverages two of the world’s most notable institutions in a way that will help foster technological innovation within New York State, while creating jobs and spurring business investment.”
“Cornell Tech is the proof that government and universities can work together to innovate and support economic growth, and we will be forever grateful for Mayor Bloomberg’s leadership in making this campus possible,” said Cornell University President David J. Skorton. “The Roosevelt Island campus is being built for the future, to be the place that generates the next big ideas, the new companies and extraordinary talent that will change New York and the world.”
“Thanks to Mayor Bloomberg’s vision, New York City is fast becoming a leading global center of innovation,” said Technion President Peretz Lavie. “Through the Joan & Irwin Jacobs Technion-Cornell Innovation Institute, our international partnership with Cornell Tech, we look forward to helping to further the city’s future as the technology capital of the world.”
Applied Sciences NYC was launched by Mayor Bloomberg in 2011 in an effort to capitalize on the considerable recent growth and even larger opportunity for future growth in technology-related jobs and businesses in New York City, and builds on the Bloomberg Administration’s record of creating a more diversified economy for the City’s future. In July 2011, NYCEDC issued an RFP seeking a university, institution or consortium to develop and operate a new or expanded campus in the City in exchange for City capital, access to City-owned land and the full support and partnership of the Bloomberg Administration, and subsequently received seven responses from 17 world-class institutions from around the globe. Cornell Tech was the first of four Applied Sciences projects to be announced by the City in an effort to strengthen New York City’s global competiveness – including its growing technology sector – and ensure that the City establishes itself as a worldwide hub of science, research, innovation and urban solutions for the digital age and the information economy. Cornell Tech was selected for this initiative based on its innovative model for graduate technology education and its emphasis on the intersections between academia and industry and forward-thinking areas of study. When completed, the new Roosevelt Island campus alone will nearly double the number of full-time, graduate engineering students enrolled in leading New York City Master’s and Ph.D. programs.
The four Applied Sciences NYC projects that have been announced by the Mayor include:
Cornell Tech on Roosevelt Island
The Center for Urban Science and Progress in Downtown Brooklyn, operated by an international consortium led by New York University
The Institute for Data Sciences and Engineering at Columbia University
Carnegie Mellon University’s Integrative Media Program at Steiner Studios in the Brooklyn Navy Yard.
Collectively, the four Applied Sciences NYC projects are expected to generate more than $33.2 billion in nominal economic activity, over 48,000 permanent and construction jobs, and approximately 1,000 spin-off companies by 2046, fulfilling the initiative’s goal of dramatically transforming the City’s economy for the 21st century. These institutions are already strengthening the City’s position as a hub of science, research, innovation and world-class urban solutions in a global economy driven by technological fluency and innovation.
“Mayor Bloomberg’s Applied Sciences initiative will transform the City’s economy, doubling the number of engineering faculty and graduate students in New York City. These are the skills we need to compete in the knowledge and information economy of the 21st Century,” said Deputy Mayor for Economic Development Robert K. Steel. “The closing of the Cornell Tech lease is a major step toward that goal and I congratulate Presidents Skorton and Lavie on this critical moment in the arc of Cornell and the Technion’s history.”
“Over only two years, thanks to an unprecedented model of collaboration across City and State government, top academic institutions, and the private sector, we have transformed Applied Sciences NYC from a visionary idea into a physical reality that is already reshaping our City,” said NYCEDC President Kyle Kimball. “Since selecting Cornell and the Technion as our first winners, in partnership with the Health and Hospitals Corporation we have built and opened a new hospital in Harlem that is currently serving former Coler-Goldwater patients; secured all necessary approvals for the Roosevelt Island campus; selected three additional Applied Sciences winners; and launched classes. Thanks to Mayor Bloomberg’s leadership, this initiative will create jobs, businesses, and technologies, resulting in transformative economic activity that will help secure the City’s future.”
“Cornell Tech is extremely grateful for the unwavering support of the Roosevelt Island community throughout the public review process and we are committed to being great neighbors during construction and beyond,” said Cornell Tech Vice President Cathy S. Dove. “We are also fortunate to have such extraordinary development partners in Forest City Ratner and Hudson/Related to help us make this vision a reality.”
“We are thrilled to be working with Cornell and so many great partners to help create a truly extraordinary new place on Roosevelt Island,” said Forest City Ratner Companies President and CEO MaryAnne Gilmartin. “Under Mayor Bloomberg’s watch the City’s tech sector has grown enormously and we are well poised as a company and as a project to continue with that growth at Cornell Tech.”
“With Mayor Bloomberg’s vision guiding the way, Cornell Tech will be at the leading edge of the next generation in tech and applied sciences,” said David Kramer, partner of The Hudson Companies. “We look forward to bringing out-of-the-box thinking to a best-in-class building on the forefront of design and sustainability.”
“I am pleased to join Mayor Bloomberg for this monumental step toward making the Cornell Tech campus a reality. I have strongly supported bringing Cornell Tech to Roosevelt Island from the very beginning of this process,” said U.S. Representative Carolyn Maloney. “The campus holds great promise for Roosevelt Island and for New York City, attracting future leaders in the technology and engineering industry. Many of the amenities included in the plans will be open and available to the public, including areas of park space. I commend Cornell for its transparency during the planning process and commitment to being a good neighbor to Island residents.”
“Cornell Tech will generate opportunities and innovations for generations to come, and today we take a step closer to our city’s future,” said Council Member Jessica Lappin.
“I applaud Mayor Bloomberg, Cornell Tech, and the Roosevelt Island Operating Corporation on their historic lease signing to build a new applied sciences campus on Roosevelt Island,” said Manhattan Borough President-Elect Gale A. Brewer. “This partnership will play a key role in the growth of New York City’s tech sector in the coming years, and will attract new development to Roosevelt Island. I look forward to working with all parties to ensure the success of this venture.”
Academic uses of the campus are anticipated to include classrooms, laboratories, teaming areas, and lecture halls, as well as start-up incubator/accelerator space to encourage entrepreneurship. The remainder of the space in the campus will be devoted to corporate co-location space designed to facilitate the interaction between academia and industry, residential uses, an executive education center, and ancillary uses, such as retail in support of the faculty, staff and students on the campus, as well as the creation of new open space.
While planning is underway for the opening of the permanent campus in 2017, Cornell Tech is already operating in temporary space in Manhattan. The campus master plan, designed by Skidmore, Owings and Merrill with James Corner Field Operations, includes a number of innovative features and facilities across a river-to-river campus with expansive views, a series of green, public spaces, and a seamless integration of indoor and outdoor areas. Cornell Tech will combine cutting edge technologies to create one of the most environmentally friendly and energy-efficient campuses in the world, not only employing, but developing new environmental technology.
A sustainable and innovative academic building will be designed by Pritzker Prize-winning architect Thom Mayne of Morphosis Architects and, in a significant departure from traditional academic facilities, take its cue from the tech world by offering open-plan space and extensive collaborative workspaces. The phase one academic building, if completed today, would be the largest net-zero energy building in eastern United States, with all of its power generated on campus.
A corporate co-location building, designed by Weiss/Manfredi and developed by Forest City Ratner Companies, will bring together corporate innovators, world-class researchers and energetic start-ups under one roof, a concrete reflection of the campus’ mission of fusing academia and industry to encourage innovation for the public good. Cornell Tech will be an anchor tenant. Renderings of this building and the academic building were released today, and are available at tech.cornell.edu/press/.
Ensuring that the campus is active 24/7, a residential building, designed by Handel Architects and developed by Hudson and Related Companies, will be built to provide convenient and affordable campus housing for students, faculty and staff. It will rely on passive sustainable design features to reduce energy usage and further advance the campus’ sustainability goals.
Plans are also under underway for an Executive Education Center and Hotel, which will help ensure that Cornell Tech is a magnet in New York City for innovation by providing conference, executive program and academic workshop space along with a hotel and destination restaurant.
The 12-acre footprint of the Cornell Tech campus includes the site of the former Goldwater Specialty Hospital and Nursing Facility, which has been replaced by the new state-of-the art, 365-bed, $300 million Henry J. Carter Specialty Hospital in Harlem, built by NYCEDC, which is operated by the NYC Health and Hospitals Corporation and provides world-class medical care for New Yorkers in need of highly specialized, complex treatment. Former Goldwater patients were relocated to the new hospital last month. The campus footprint also includes property formerly controlled by the Roosevelt Island Operating Corporation. Cornell Tech has spent the past year working with the Roosevelt Island community on plans to minimize the impact of construction on residents, including deployment of the largest barging program in New York City to remove demolition materials from the site.
Cornell Tech classes began earlier this year in space donated by Google in Chelsea. The school now includes masters and Ph.D. students, world-class faculty and established collaborations with dozens of industry-leading organizations contributing to graduate study in areas such as Computer Science, Electrical and Computer Engineering, Information Science, Operations Research and Business. Cornell Tech also launched its commitment to partnership with New York City’s public school students earlier this year, working with numerous organizations to bring tech education to a diverse audience. A director of K-12 education for Cornell Tech will be announced early in 2014.
Beginning in January, the Joan and Irwin Jacobs Technion-Cornell Innovation Institute at Cornell Tech will welcome a number of postdoctoral students to the current campus. Later in 2014, the Jacobs Institute will launch a master’s degree program in Connective Media designed to educate the entrepreneurial engineers and technologists needed in the media sector to steward the continuing digital transformation of the industry. Students in this two-year program will receive degrees from both Technion and Cornell. Also in 2014, Cornell Tech will launch a Johnson MBA that will combine business, technology, innovation and entrepreneurship in a fast-paced, hands-on learning environment.
Cornell Tech will host entrepreneurs-in-residence, organize business competitions, provide legal support for startups, reach out to existing companies to form research partnerships and sponsor research, and establish a pre-seed financing program to support promising research. In addition, the campus will structure its on-site tech transfer office to facilitate startup formation and technology licensing. Cornell Tech will also invest $150 million that will be solely devoted to start-up businesses in the City.
In keeping with the focus on community involvement contained in the RFP, the Cornell Tech proposal outlined a number of areas in which the universities will touch the lives of New Yorkers — the type of involvement to which both schools have been committed for many years in their primary campus communities. Plans for community involvement in New York City include the creation of education enhancement programs that will impact a minimum of 10,000 New York City students and 200 New York City teachers per year. Cornell Tech also intends to work closely with PS/IS 217 on Roosevelt Island to enrich their curricula and participate in STEM-oriented programming. They will also work to meet the goals of the City’s HireNYC employment program and develop partnerships for job placement and training. In furtherance of its community outreach goals, Cornell Tech will offer significant programming on and off its campus designed to engage with residents of Roosevelt Island and the larger City. Cornell’s campus plan will further create new public open space on the campus.
Technion-Cornell Innovation Institute: momentous gift of $133 million to create the Joan and Irwin Jacobs Technion-Cornell Innovation Institute (JTCII)
Reporter: Aviva Lev-Ari, PhD, RN
We are pleased to share some exciting news
Irwin and Joan Jacobs on the Technion campus
Technion Guardians Joan and Irwin Jacobs, of San Diego, have made a momentous gift of $133 million to name the Technion-Cornell Innovation Institute. Dr. Irwin Jacobs, Founding Chairman and CEO Emeritus of Qualcomm, and his wife Joan will create the Joan and Irwin Jacobs Technion-Cornell Innovation Institute (JTCII). The JTCII is a key component of Cornell Tech, whose permanent campus will eventually be located on Roosevelt Island. The funds will help support curriculum initiatives, faculty and graduate students, and industry interactions in a two-year graduate program.
The gift is being announced today by New York City Mayor Michael R. Bloomberg during a press conference at New York City Hall, together with Joan and Irwin Jacobs, Technion President Peretz Lavie and Cornell President David J. Skorton. You can view the press conference at: www.nyc.gov starting at 3:00 p.m. EDT.
The Jacobses are both Cornell alumni who have a long history of supporting both institutions. Their visionary support of the Technion includes the Irwin and Joan Jacobs Graduate School and the Irwin and Joan Jacobs Center for Communications and Information Technologies. A member of the Technion International Board of Governors, Dr. Jacobs is a Life Trustee of the American Technion Society National Board of Regents, and a member of the ATS San Diego Chapter. He received the ATS’ highest honor, The Albert Einstein Award, in 1996, and a Technion Honorary Doctorate in 2000.
The JTCII plans to offer a two-year interdisciplinary program where students concurrently earn dual master’s degrees — one from Cornell and one from the Technion. This degree program will allow students to specialize in applied information-based sciences in one of three hubs focused around leading New York City industries — Connective Media, Healthier Living and The Built Environment — while honing their entrepreneurial skills. The first area of specialization will be in Connective Media, and is slated to begin in the fall of 2014. Research will also be focused on the hub areas.
A novel program for Postdoctoral Innovation Fellows will launch in fall 2013. The aim is to support individuals who seek to commercialize their research ideas in the stimulating environment of the JTCII, while taking full advantage of the entrepreneurial network of Cornell Tech and the proximity to New York City-based markets. Dr. Jacobs, along with Mayor Michael R. Bloomberg and Google Executive Chairman Eric Schmidt, serves as an advisor to Cornell Tech, the overall campus that is part of Cornell University.
Technion: Israel’s Hard Drive — as published in NY TimesIn case you missed it, The New York Times published a wonderful article about the Technion, featured on the cover page of its Education Life section on April 14, 2013. The article credits the Technion for transforming the once quiet city of Haifa into a high-tech center.Click here to read the storyClick here to read a NY Times story on Cornell Tech
The Joan and Irwin Jacobs Technion–Cornell Innovation Institute (JTCII) is an academic partnership between two of the world’s most distinguished academic institutions, the Technion – Israel Institute of Technology and Cornell University.
The JTCII is a central component of the new Cornell Tech campus in New York City. It will offer unique graduate degree programs and foster applied research by faculty, students and fellows, in collaboration with industry partners.
JOAN AND IRWIN JACOBS
On April 22, Dr. Irwin Mark Jacobs, Founding Chairman and CEO Emeritus of Qualcomm, and his wife Joan Klein Jacobs, announced a $133 million gift to Cornell University and the Technion-Israel Institute of Technology to create the Joan and Irwin Jacobs Technion-Cornell Innovation Institute.
The Jacobses are both Cornell alumni who have a long history of supporting both Cornell and the Technion-Israel Institute of Technology. They have established the Irwin M. and Joan K. Jacobs Scholars and Fellows Programs and the Irwin and Joan Jacobs Professorship, both in the College of Engineering, as well as the Joan Klein Jacobs Cornell Tradition Fellowship in the College of Human Ecology at Cornell. Dr. Jacobs is a former member of the Cornell University Council and Mrs. Jacobs served on the President’s Council of Cornell Women. In recognition of their distinguished service to Cornell, Dr. and Mrs. Jacobs were both elected Presidential Councillors in 2005. The Jacobses’ visionary support of the Technion includes the Irwin and Joan Jacobs Graduate School and the Irwin and Joan Jacobs Center for Communications and Information Technologies. A member of the Technion International Board of Governors, Dr. Jacobs is a Life Trustee of the American Technion Society National Board of Regents, and a member of the ATS San Diego Chapter. Dr. Jacobs, along with Mayor Michael R. Bloomberg and Google Executive Chairman Eric Schmidt, is a member of Cornell Tech’s Steering Committee.
Dr. and Mrs. Jacobs are among the world’s most generous philanthropists. Their support has had a significant impact on numerous cultural, medical, educational, and civic organizations. The engineering school at the University of California, San Diego bears Dr. and Mrs. Jacobs’ names, as do the performing arts center of the campus’ La Jolla Playhouse and the new UCSD Medical Center.
PROGRAMS & RESEARCH
The JTCII fuses academic excellence with real-world applications through its unique two-year dual master’s degree program. The first class of students will begin in the Fall of 2014. Prospective JTCII faculty members will be accomplished scientists, engineers and technologists with proven entrepreneurial skills who can effectively engage with industry.
The JTCII departs from traditional academic departments and is organized in interdisciplinary hubs selected for their relevance to the New York City economy. The three hub areas are: Connective Media, which focuses on mobile and interactive media; Healthier Life, which will create solutions for better health care outcomes; and the Built Environment, which aims to increase the efficiency and sustainability of large-scale urban environments. In addition, a dynamic Industrial Affiliates program will provide a valuable source of local experts and seasoned entrepreneurial mentors.
In Fall 2013, the JTCII will launch a Postdoctoral Innovation Fellows program to encourage entrepreneurial efforts among highly qualified scientists. The program will provide fellows with rich ties to the emerging New York City tech ecosystem, access to industrial mentors and seasoned entrepreneurs, and connections to the local venture capital and legal communities.
Founding Director, Joan and Irwin Jacobs Technion-Cornell Innovation Institute
Daniel Huttenlocher
Dean and Vice Provost, Cornell Tech
David J. Skorton
President, Cornell University
Peretz Lavie
President, Technion – Israel Institute of Technology
Board of Directors
CHAIRKent FuchsProvost, Cornell University
Arnon BenturExecutive Vice President and Director General, Technion-Israel Institute of Technology
Lance CollinsDean of the College of Engineering, Cornell University
Joanne DeStefanoVice President for Finance and Chief Financial Officer, Cornell University
Moshe EizenbergProfessor (Emeritus) of Materials Engineering and Former Vice President for Research, Technion-Israel Institute of Technology
Paul FeiginSenior Executive Vice President, Technion-Israel Institute of Technology
Daniel HuttenlocherDean and Vice Provost, Cornell Tech
Adam ShwartzChair of the Department of Electrical Engineering, Technion-Israel Institute of Technology
WHY NYC?
In 2010, the City of New York launched its groundbreaking Applied Sciences NYC program, an unparalleled opportunity to build world-class applied sciences and engineering campuses.
With Applied Sciences NYC, the city’s Economic Development Corporation seeks to dramatically expand capacity in the applied sciences to maintain global competitiveness and create jobs. By creating campuses like Cornell Tech, innovative new ideas lead to spinoff companies right here in the city that will transform its economy. The next high growth company—a Google, Amazon, or Facebook—may emerge in NYC.
ABOUT THE PARTNERS
Cornell University
Cornell University, one of the world’s powerhouse universities, is both a private university and a land grant institution of New York State, with 21,400 students in Ithaca, New York, Weill Cornell Medical College in New York City and Qatar, United Arab Emirates. An Ivy League institution, Cornell awarded the nation’s first university doctorate degrees in electrical engineering and industrial engineering. There are forty Nobel Laureates with Cornell affiliations.
Technion – Israel Institute of Technology
Technion-Israel Institute of Technology is a major source of the innovation and brainpower that drives the Israeli economy, and the cornerstone of Israel’s renown as the world’s “Start-Up Nation.” Alongside this, its three Nobel Prize Laureates exemplify traditional academic excellence. Technion people, ideas and inventions make important contributions to the world, including life-saving medicine, sustainable energy, computer software, water conservation and nanotechnology.
FIND MORE INFORMATION
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The Technion – Israel Institute of Technology was today ranked 6th in the world by a survey conducted by MIT. The study evaluated entrepreneurship and innovation in higher education institutions worldwide. The ranking was compiled by 61 experts from 20 different countries. It identified 120 universities which demonstrate “a decisive impact and significant contribution in the field of entrepreneurship and innovation.”
Technion followed MIT, Stanford, Cambridge, Imperial College and Oxford, but preceded the University of San Diego, Berkeley, ETH Swiss and the National University of Singapore. The report also placed Israel 3rd in terms of entrepreneurship and innovation, after the US and the UK, but ahead of Sweden, Singapore, Germany, the Netherlands, China and Canada.The survey, which was carried out in partnership with the Skolkovo Institute of Science and Technology in Russia, also placed the Technion first in the category of universities that create or support technological innovation even though they operate in a challenging environment.
Instituting an institutional E&I culture – for entrepreneurship and innovation – is considered among experts as the essential ingredient for sustaining a successful system. In this respect, the Technion is mentioned as an institution that possesses the ethos of aspiration and achievement.
This is the first stage (out of three) in the comprehensive survey. In his reaction to these most favorable results, Technion President Professor Peretz Lavie said, “Technion’s position among the top ten leading universities in the world in the areas of innovation and entrepreneurship brings us closer to fulfilling our mission goals: to be counted among the top ten leading universities in the world. This is not the first time the Technion has earned international acclaim such as this,” he continued. “The university’s contribution to Israel’s advanced technology industry is recognized around the world. Not by coincidence did we prevail in the New York City’s tender last year to establish a scientific-engineering research center in partnership with Cornell University. The city’s mayor, Michael Bloomberg, said then that the Technion is the only university in the world capable of successfully turning the economic tide of an entire country, from exporters of citrus fruit to a global center for advanced industry and an authority of knowledge. To date, 61 experts from around the world have endorsed this statement.”
The Technion-Israel Institute of Technology is a major source of the innovation and brainpower that drives the Israeli economy, and a key to Israel’s reputation as the world’s “Start-Up Nation.” Its three Nobel Prize winners exemplify academic excellence.
Prof. Beth Murinson, MD, PhD, at Technion’s Rappaport Faculty of Medicine, has been a very busy person since coming to Israel in 2010 with her husband and two children. Before Technion she was an associate professor at Johns Hopkins Medical School. A neurologist who specializes in injury to the peripheral nerve, these days Murinson can be found in her laboratory and at Rambam hospital. She conducts research and works on educational projects that are designed to treat patients with acute and persistent pain; teaches medical students, both the Israeli students and those from the USA who are in TeAMS – Technion’s American medical school program; advises medical students in the USA; is an attending neurologist in the Department of Neurology at Rambam Health Care Campus and runs an outpatient clinic specializing in peripheral nerve injuries, chronic neuropathic pain and back injuries.
Murinson’s research is focused on chemotoxic and traumatic injuries to the nerve. Her two main research models address the response of growing peripheral nerve cells to exposure to a common pharmacological agent and deal with nerve injury. She is trying to determine what is the least amount of injury that will produce neuropathic pain; it is important to understand what injuries are painful and which injuries are not. Her goal is to find methodology or treatments that will help prevent induced nerve injury. There are some drugs that are widely used and taken by millions of people that have the potential to harm nerves. She also works in collaboration with the oncology group at Rambam.
“To find methodology or treatments that will help prevent induced nerve injury.”
Murinson’s academic credentials are impressive; she got an early start by graduating high school early and proceeding to receive her Bachelor’s degree in mathematics from Johns Hopkins, a Master’s from UCLA in biomathematics, and an MD/Phd (in physiology) from the University of Maryland, graduating with honors. After, she did her residency in neurology at Yale and she finished her education with a fellowship in neuroelectrophysiology back at Johns Hopkins.
It’s a wonder she found time to write a book.
Take Back Your Back is the volume to read if you are suffering from back pain. The book lets patients know everything they can do to regain control over their lives after a back injury. It provides a wealth of information on what can go wrong with the back and how patients can take charge of their own recovery.
Cerebral ischemic disorders are one of the main causes of death. In brain ischemia, blood flow disruptions limit the supply of oxygen and glucose to neurons, initiating excitotoxic events.
Bioactivity-guided fractionation of an alcohol extract of the soft coral Sarcophyton glaucum collected from the intertidal areas and the fringing coral reefs near Hurghada, Red Sea, Egypt resulted in the isolation of a new lactone cembrane diterpene, sarcophytolide. The structure of this compound was deduced from its spectroscopic data and by comparison of the spectral data with those of known closely related cembrane-type compounds. In antimicrobial assays, the isolated compound exhibited a good activity towards Staphylococcus aureus, Pseudomonas aeruginosa, and Saccharomyces cerevisiae. Sarcophytolide was found to display a strong cytoprotective effect against glutamate-induced neurotoxicity in primary cortical cells from rat embryos. Preincubation of the neurons with 1 or 10 microg/ml of sarcophytolide resulted in a significant increase of the percentage of viable cells from 33 +/- 4% (treatment of the cells with glutamate only) to 44 +/- 4 and 92 +/- 6%, respectively. Administration of sarcophytolide during the post-incubation period following glutamate treatment did not prevent neuronal cell death. Pretreatment of the cells with sarcophytolide for 30 min significantly suppressed the glutamate-caused increase in the intracellular Ca2+ level ([Ca2+]i). Evidence is presented that the neuroprotective effect of sarcophytolide against glutamate may be partially due to an increased expression of the proto-oncogene bcl-2. The coral secondary metabolite, sarcophytolide, might be of interest as a potential drug for treatment of neurodegenerative disorders.
Pharmacological treatment of Alzheimer disease: From psychotropic drugs and cholinesterase inhibitors to pharmacogenomics
For the past 20 years the scientific community and the pharmaceutical industry have been searching for treatments to neutralize the devastating effects of Alzheimer disease (AD). During this period important changes in the etiopathogenic concept of AD have occurred and, as a consequence, the pharmacological approach for treating AD has also changed. During the past 2 decades only 3 drugs for AD have been formally approved by the FDA, although in many countries there are several drugs which are currently used as neuroprotecting agents in dementia alone or in combination with cholinesterase inhibitors. The interest of the pharmaceutical industry has also shifted from the cholinergic hypothesis which led to the development of cholinesterase inhibitors to enhance the bioavailability of acetylcholine at the synaptic cleft to a more “molecular approach” based on new data on the pathogenic events underlying neurodegeneration in AD.
In our opinion, the pharmacological treatment of AD should rely on a better understanding of AD etiopathogenesis in order to use current drugs that protect the AD brain against deleterious events and/or to develop new drugs specifically designed to inhibit and/or regulate those factors responsible for premature neuronal death in AD. The most relevant pathogenic events in AD can be classified into 4 main categories:
secondary events (beta-amyloid deposition in senile plaques and brain vessels, neurofibrillary tangles due to hyperphosphorylation of tau proteins, synaptic loss),
All of these pathogenic events are potential targets for treatment in AD. Potential therapeutic strategies for AD treatment include palliative treatment with nonspecific neuroprotecting agents, symptomatic treatment with psychotropic drugs for noncognitive symptoms, cognitive treatment with cognition enhancers, substitutive treatment with cholinergic enhancers to improve memory deficits, multifactorial treatment using several drugs in combination and etiopathogenic treatment designed to regulate molecular factors potentially associated with AD pathogenesis.
This review discusses the conventional cholinergic enhancers (cholinesterase inhibitors, muscarinic agonists), noncholinergic strategies that have been developed with other compounds, novel combination drug strategies and future trends in drug development for AD treatment.
Stem-cell activation,
genetically manipulated cell transplantation,
gene therapy and
antisense oligonucleotide technology
constitute novel approaches for the treatment of gene-related brain damage and neuroregeneration.
The identification of an increasing number of genes associated with neuronal dysfunction along the human genome together with the influence of specific allelic associations and polymorphisms indicate that pharmacogenomics will become a preferential procedure for drug development in polygenic complex disorders. Furthermore, genetic screening of the population at risk will help to identify candidates for prevention among first-degree relatives in families with transgenerational dementia.
Dementia is a major problem of health in developed countries. Alzheimer’s disease (AD) is the main cause of dementia, accounting for 50–70% of the cases, followed by vascular dementia (30–40%) and mixed dementia (15–20%). Approximately 10–15% of direct costs in dementia are attributed to pharmacological treatment, and only 10–20% of the patients are moderate responders to conventional anti-dementia drugs, with questionable cost-effectiveness. Primary pathogenic events underlying the dementia process include genetic factors in which more than 200 different genes distributed across the human genome are involved, accompanied by progressive cerebrovascular dysfunction and diverse environmental factors. Mutations in genes directly associated with the amyloid cascade (APP, PS1, PS2) are only present in less than 5% of the AD population; however, the presence of the APOE-4 allele in the apolipoprotein E (APOE) gene represents a major risk factor for more than 40% of patients with dementia. Genotype–phenotype correlation studies and functional genomics studies have revealed the association of specific mutations in primary loci (APP, PS1, PS2) and/or APOE-related polymorphic variants with the phenotypic expression of biological traits. It is estimated that genetics accounts for 20–95% of variability in drug disposition and pharmacodynamics. Recent studies indicate that the therapeutic response in AD is genotype-specific depending upon genes associated with AD pathogenesis and/or genes responsible for drug metabolism (CYPs). In monogenic-related studies, APOE-4/4 carriers are the worst responders. In trigenic (APOE-PS1-PS2 clusters)-related studies the best responders are those patients carrying the 331222-, 341122-, 341222-, and 441112- genomic profiles. The worst responders in all genomic clusters are patients with the 441122+ genotype, indicating the powerful, deleterious effect of the APOE-4/4 genotype on therapeutics in networking activity with other AD-related genes. Cholinesterase inhibitors of current use in AD are metabolized via CYP-related enzymes. These drugs can interact with many other drugs which are substrates, inhibitors or inducers of the cytochrome P-450 system; this interaction elicits liver toxicity and other adverse drug reactions. CYP2D6-related enzymes are involved in the metabolism of more than 20% of CNS drugs. The distribution of the CYP2D6 genotypes differentiates four major categories of CYP2D6-related metabolyzer types: (a) Extensive Metabolizers (EM)(*1/*1, *1/*10)(51.61%); (b) Intermediate Metabolizers (IM) (*1/*3, *1/*4, *1/*5, *1/*6, *1/*7, *10/*10, *4/*10, *6/*10, *7/*10) (32.26%); (c) Poor Metabolizers (PM) (*4/*4, *5/*5) (9.03%); and (d) Ultra-rapid Metabolizers (UM) (*1xN/*1, *1xN/*4, Dupl) (7.10%). PMs and UMs tend to show higher transaminase activity than EMs and IMs. EMs and IMs are the best responders, and PMs and UMs are the worst responders to pharmacological treatments in AD. It seems very plausible that the pharmacogenetic response in AD depends upon the interaction of genes involved in drug metabolism and genes associated with AD pathogenesis. The establishment of clinical protocols for the practical application of pharmacogenetic strategies in AD will foster important advances in drug development, pharmacological optimization and cost-effectiveness of drugs, and personalized treatments in dementia.
This manuscript reviews the preclinical in vitro, ex vivo, and nonhuman in vivo effects of psychopharmacological agents in clinical use on cell physiology with a view toward identifying agents with neuroprotective properties in neurodegenerative disease. These agents are routinely used in the symptomatic treatment of neurodegenerative disease. Each agent is reviewed in terms of its effects on pathogenic proteins, proteasomal function, mitochondrial viability, mitochondrial function and metabolism, mitochondrial permeability transition pore development, cellular viability, and apoptosis. Effects on the metabolism of the neurodegenerative disease pathogenic proteins alpha-synuclein, beta-amyloid, and tau, including tau phosphorylation, are particularly addressed, with application to Alzheimer’s and Parkinson’s diseases. Limitations of the current data are detailed and predictive criteria for translational clinical neuroprotection are proposed and discussed. Drugs that warrant further study for neuroprotection in neurodegenerative disease include pramipexole, thioridazine, risperidone, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, fluoxetine, buspirone, clonazepam, diphenhydramine, and melatonin. Those with multiple neuroprotective mechanisms include pramipexole, thioridazine, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, clonazepam, and melatonin. Those best viewed circumspectly in neurodegenerative disease until clinical disease course outcomes data become available, include several antipsychotics, lithium, oxcarbazepine, valproate, several tricyclic antidepressants, certain SSRIs, diazepam, and possibly diphenhydramine. A search for clinical studies of neuroprotection revealed only a single study demonstrating putatively positive results for ropinirole. An agenda for research on potentially neuroprotective agent is provided.
RESULTS
The preclinical investigation of the impact of psychotropic drugs on molecular processes pertinent to neuroprotection varied considerably. For example, regarding dopamine agonists, we identified one paper addressing impact on αSyn, two on Aβ, one on mitochondrial function, eight on the permeability transition pore, and eight on apoptosis. No papers were identified addressing the impact of these drugs on tau, proteasomes, or cell viability. By comparison, with regard to antipsychotics, we identified six papers addressing effects on Aβ, five on tau, four on proteasomes, 28 on mitochondrion, 25 on permeability transition pore, 11 on cell viability, and 45 on apoptosis, yet no papers discussed the impact of these agents on αSyn. Only 10 total papers were identified addressing the effects of all these psychotropics on ubiquitin—one indication of the weakness of the literature in certain areas. In addition, there was considerable variability in the laboratory approaches, models, and assays utilized to examine the impact on a given molecular process. For instance, studies of mitochondrial effects used mouse, rat, or human brain cell cultures, mouse or human heart, liver or endothelial cells, and normal or neoplastic leukocytes. These studies variously assessed oxygen uptake, Complex I, II, IV, or V activity, ATP production, succinate production or succinate dehydrogenase activity, redox reaction velocity, reactive oxygen species production, and/or morphological changes on electron microscopy. Even within the papers that focused on human brain cells, different models used a variety of neuron types including those from brainstem, basal ganglia, cerebellum, and several regions of the cortex. We organized and summarized the available data making no assumptions about relative predictive translational neuroprotective merits of different models and tissues, which are not known at present (see discussion).
The most important detailed findings for each drug are briefly summarized in Table 1, Table 2, Table 3, and Table 4 (located online at http://neuro.psychiatryonline.org/cgi/content/full/22/1/8/DCI). The recently discovered TDP-43 was also considered while this project was underway, but no relevant articles were evident for this protein.
DISCUSSION
It is evident from the above that there is significant variation in degree of investigation, cell lines studied, and methodological approaches. Other limitations include the varying use of neural tissues, variance in the neuronal types studied, use of neuroblastoma lines instead of neurons, study of immature or poorly differentiated cells that may be more prone to apoptosis than more mature cells, and the infrequent characterization of effects on αSyn, tau, and Aβ. Such deficiencies in the data significantly confound the ability to draw definitive conclusions. In particular, the deficiencies in the data raise the question as to the most valid, clinically relevant, and appropriate standards of evidence to apply in determining which preclinical findings will predictably translate into clinical neuroprotection in patients with neurodegenerative diseases.
A number of concerns impact the selection of an appropriate standard of evidence. First, there are no established general criteria for judging preclinical neuroprotective data across the diversity of neurodegenerative diseases. Second, unlike clinical evidence-based medicine (EBM) standards, there do not appear to be established uniform criteria for judging the diversity of preclinical findings. From an EBM perspective, the data considered here are even less compelling than Class II or IV18 or Level C19clinical case reports since they generally do not pertain to findings in human patients. Third, there are considerable variabilities across the present preclinical findings with respect to intra- and extramodel replication, replications in neural tissue, the specific neural tissues studied, and the specific brain locus even when neurons are consistently studied. These are summarized in Table 5. Fourth, replications are still needed using the same physiological dose range, particularly because some have observed bell—shaped rather than sigmoid—shaped neuroprotective dose—response curves.20,21 Fifth, some drugs have mixed actions, simultaneously possessing some neuroprotective actions and other neurodegenerative actions. It is not yet clear whether the various actions should receive equal weight or whether one may trump others (for example, effects on apoptotic measures may be more determinative in importance than effects on more “upstream” processes such as mitochondrial potential or proteasomal function). Sixth, there is no gold-standard preclinical model but, instead, a diversity of models that each have their own select benefits and limitations. These and other factors likely contribute to the current disconnect between preclinical findings and neuroprotective clinical trial results.
Some criteria for considering neuroprotective candidate agents have been elaborated in Parkinson’s disease22 and stroke.23 In Parkinson’s disease, scientific rationale, penetration of the blood-brain barrier, safety and tolerability, and efficacy in relevant animal models of the disease or an indication of benefit in human clinical studies constitute criteria.22 In the case of FDA-approved psychotropics reviewed here, which essentially meet most of these criteria (with the exception of systematic, consistent application in relevant neurodegenerative disease models), the question then becomes: how good is the available preclinical evidence of neuroprotection? Ravina et al.22 noted that the most problematic issue in Parkinson’s disease was evaluating animal data given the many different models that were of uncertain value in predicting results in humans and noted further that a clinical trial would actually be needed to demonstrate the predictive validity of any preclinical model. Similarly, it is not possible to judge the quality of the present preclinical findings by the models used because the predictive validities of the models remain unclear. In stroke,23 potentially successful drug candidates have been considered to be inferable from preclinical data by the following criteria: (a) adequately defined dose-response relations; (b) time window studies showing a benefit period; (c) adequate physiological monitoring in unbiased, replicated, randomized, blinded animal studies; (d) lesion volume and functional outcome measures determined acutely and at longer term followup; (e) demonstration in two animal species; (f) submission of findings to a peer-reviewed journal. However, even with these criteria, Gladstone et al.24 have pointed out that translation of preclinical findings to clinical efficacy has been hampered by a lack of functional outcomes, long-term end points, permanent ischemia models, extended time windows, and selective white matter evaluation in preclinical models whereas clinical studies are plagued by insensitive outcome measures, lack of stroke subtype specificity, and inattention to the ischemic penumbra, among other concerns. Ford25 has also pointed out that a number of compounds fulfilling these stroke neuroprotectant criteria have failed to afford translational clinical neuroprotection. Analogous concerns obtain for neurodegenerative disease preclinical models and clinical methods, particularly whether putative criteria will reliably predict translation to clinical neuroprotection. Additionally, a nearly endless array of clinical variables including gender, age, pharmacogenomics, medical history, coadministered drugs, and other factors may contribute to an inability to predict clinical neuroprotection despite preclinical success. Thus, predictive criteria remain in need of development.
Reflection upon these translational issues in regard to psychotropic neuroprotection in neurodegenerative diseases first suggests the need for replication within and between specific preclinical models in specific neurons at specific loci to elucidate physiological dose-response relations that should then themselves be replicated as a first step. Additionally, other issues seem relevant to the problem of determining which candidate drugs may be most likely to effect clinical neuroprotection. We suggest preliminary neuroprotective drug selection criteria for assessing the likelihood of translational clinical neuroprotection in neurodegenerative diseases (Table 6). These criteria, including preclinical (at least two replicated neuroprotective actions at physiological doses in an established neuroprotective model, neural tissue, and disease-specific animal model in excess of the number of known neurodegenerative actions) and clinical (delayed progression on clinical markers and unexpected benign disease course not accounted for by symptomatic properties) criteria, can be evaluated over time and modified as future data indicate. Given the lack of information regarding the utility of specific preclinical paradigms in predicting clinical neuroprotective effects, it is premature to rank or weight these criteria. Rather, recent concerns26 notwithstanding and until a better study methodology is developed, we suspect that the greater the number of criteria met by a candidate drug, the greater the likelihood of demonstrating translational clinical neuroprotective efficacy in a randomized, double-blind, placebo-controlled, delayed-start or randomized-withdrawal clinical trial.27 Such trials are needed because agents deemed promising based upon preclinical data often fail to demonstrate neuroprotection in clinical trials for reasons identified in the above paragraph. At present, preclinical demonstration of replicable neuroprotective effects in neural tissues at clinically-relevant doses does not assure a positive result in a clinical trial, nor does the absence of such evidence necessarily exclude clinical neuroprotective benefits. Until such clinical findings obtain, it is impossible to identify preclinical determinants predictive of translational clinical success and ascertain whether patients are actually being helped or harmed in a neuroprotective sense by the use of these drugs.
Beyond the methodological concerns expressed above, a practical assessment of these preclinical findings is still possible. Given the relative infancy of this field of research, the present state of the literature, the limitations of the data described above, and our current ignorance of preclinical evidence predictive of successful clinical translation, there is the very real possibility of prematurely disregarding findings that may ultimately prove to be of clinical significance with further research (a “type II” error) by applying an overly stringent standard of evidence. It seems that, at the present time, the proper approach is to instead look at the preponderance of the available findings and attempt some generalizations that constitute general impressions to be tested in future research, similar to the process of developing and refining clinical diagnostic criteria. Accordingly, the following observations are drawn from looking at all of the studies, without any exclusions, except where there are clearly contradictory data. As noted, many of the findings have not yet been independently replicated in the same model despite apparent replication in a different model (Table 5). Until the state of the literature develops to the point where independent replications in the same model are routinely observed, appropriate assessment criteria must be very liberal, resulting in conclusions that can only be viewed as preliminary. Adopting this approach with its attending caveats, some preliminary observations can be gleaned from the data. Below, we first consider drugs with respect to their neuroprotective potentials, distinguishing drugs meriting further study from those that have limitations dissuading further investigation and those for which too little data are available to form any conclusions. (We also summarize neuroprotective effects by drug class in Appendix 1 and drugs by neuroprotective actions in Appendix 2 [located online at http://neuro.psychiatryonline.org/cgi/content/full/22/1/8/DCI%5D; Part 2 of this report focuses on the broader neuroprotective aspects of selected psychopharmacological classes.) Next, we assess the general properties of the various classes of psychotropics. We then consider each investigated cellular function with regard to the drugs that influence them. Finally, we detail a research agenda for drugs of interest and consider the progress made in clinical neuroprotective trials thus far, recommending a next step in their development.
Drugs of Neuroprotective Interest
Drugs meriting further study include:
pramipexole,
thioridazine,
risperidone,
olanzapine,
quetiapine,
lithium,
valproate,
nortriptyline,
desipramine,
maprotiline,
fluoxetine,
paroxetine,
buspirone,
clonazepam,
diphenhydramine, and
melatonin.
These are drugs with at least one significant neuroprotective action and relatively negligible countervailing neurodegeneration—promoting effects, as summarized in Table 1, Table 2, and Table 3 (especially the “Comments” column summarizing the data), and particularly Table 7 (tables located online at http://neuro.psychiatryonline.org/cgi/content/full/22/1/8/DCI).
Drugs that are not recommended for further study at the present time due to more significant limiting issues (see Table 1, Table 2, and Table 3, especially “Comments” column summarizing the data). Haloperidol does not warrant further study because of tau hyperphosphorylation, reduced cell viability, and multiple proapoptotic actions, especially in hippocampus, cortex, striatum, and nigra. Fluphenazine, chlorpromazine, and clozapine, probably do not warrant further study because of multiple proapoptotic actions, and chlorpromazine inhibits tau dephosphorylation. Carbamazepine has variable neuroprotective properties. Oxcarbazepine promotes apoptosis. Clomipramine also generally promotes apoptosis. Diazepam has mixed effects on neural apoptosis, but uncouples oxidative phosphorylation, releases cytochrome c, and promotes apoptosis in a number of neuronal models, although it promoted ATP recovery and prevented cytochrome c release in a single study of ischemic hippocampal slices.
It should be emphasized that there are no convincing clinical data at present to indicate that these drugs are unsafe for clinical use due to neurodegenerative effects, only preclinical evidence to temper enthusiasm for clinical trial application as a neuroprotectant. Until such data become available, the use of these drugs continues to be guided by clinical symptomatic indications. The limiting actions described above are considered to be significant enough to likely detract from an overall neuroprotective effect, making positive findings less likely, hence our inability to recommend them at present. It must also be recognized that some of these limitations still await replication (Table 5), and that it is presently unknown precisely which neuroprotective modes of action are positively and negatively predictive of clinical neuroprotection.
Drugs for Which Limited Data Do Not Allow Recommendations
There are currently insufficient data for ropinirole, amantadine, thiothixene, aripiprazole, ziprasidone, amitriptyline, imipramine, trimipramine, doxepin, protriptyline, bupropion, sertraline, fluvoxamine, citalopram, trazodone, nefazodone, venlafaxine, duloxetine, mirtazapine, chlordiazepoxide, flurazepam, temazepam, chlorazepate, lorazepam, oxazepam, alprazolam, zolpidem, cyproheptadine, hydroxyzine, modafinil, ramelteon, benztropine, trihexyphenidyl, and biperiden.
Briefly, regarding the neuroprotective effects of psychopharmacological classes, certain generalizations are apparent (see Appendix 1 for details). There is some evidence to suggest that D2 agonists, lithium, some SSRIs, and melatonin reduce . D2 agonists, certain atypical antipsychotics and antidepressants, and melatonin suppress . Neuroleptics, lithium, certain heterocyclic antidepressants, the central benzodiazepine receptor agonist clonazepam, and melatonin inhibit . D2 agonists, atypical antipsychotics, lithium, antidepressants, the 5HT1a agonist buspirone, and melatonin inhibit , whereas the peripheral benzodiazepine receptor agonist diazepam promotes apoptosis. These, however, are gross generalizations, which are better explained in Appendix 1 and Appendix 2. Moreover, it is potentially erroneous to project neuroprotective effects upon a pharmacological class because neuroprotective properties may not relate to their currently recognized pharmacodynamic effects.
Above, we have indicated which drugs merit further study, those which cannot be recommended due to significant limiting issues, and those with inadequate data to allow assessment. Among drugs meriting further study, Table 8 discloses the various agents along with evidential weights for their various neuroprotective actions. It can be seen that drugs that inhibit apoptosis and have at least one other general antiapoptotic action (each demonstrated by a net of two or more studies supporting a neuroprotective action, without consideration of their effects on specific proteins) include pramipexole, olanzapine, lithium, desipramine, and melatonin. The remaining agents have less robust findings supporting general neuroprotective actions. Considering the effects of these drugs on proteins and at least one other neuroprotective action in a disease-specific model, the most promising drugs in Alzheimer’s disease would include olanzapine, lithium, and melatonin while drugs with less robust support in Alzheimer’s disease include pramipexole, quetiapine, valproate, and desipramine. Applying the same criteria, drugs of promise in Parkinson’s disease include pramipexole and melatonin, while drugs with less robust support in Parkinson’s disease include olanzapine, lithium, valproate, desipramine and clonazepam. Similarly, in Huntington’s disease, desipramine is the most promising, with less robust support for lithium, valproate, nortriptyline, and maprotiline. There is some support for pramipexole, olanzapine, lithium, and nortriptyline in amyotrophic lateral sclerosis. However, as we have pointed out above, it is premature to draw any clinical conclusions from these data because of the limitations we have described and because more data will be forthcoming.
Directions for Future Research
Given this inability to draw clinical conclusions, we provide the next steps that should be undertaken in developing psychotropic research to the point that results can guide the clinical application of these drugs for neuroprotection. While it is not clear what the most predictive models of clinical neuroprotection are, and what the most important neuroprotective mechanisms are, it is apparent that some drugs are further along in their preclinical research than others. It is also clear that some seemingly paradoxical neuroprotective outcomes are seen, such as modafinil’s ability to increase glutamate release and yet reduce glutamate toxicity, and paroxetine’s ability to reduce hippocampal Aβ production in Alzheimer’s disease transgenic mice despite its anticholinergic properties that would otherwise tend to increase Aβ production. These seeming contradictions point to the need to focus on research findings rather than our current limited theoretical understanding. Thus, we outline the next research steps to be taken to elaborate findings that will move us toward establishing neuroprotective drugs that can be applied by clinicians.
Apathy Treatments
It would be of interest to investigate pramipexole in normal neurons, especially dopaminergic and cholinergic neurons.
Pramipexole should be better characterized as to its effects on αSyn, Aβ, tau, and Aβ fibril and oligomer-induced reactive oxygen species formation as well as on the proteasome and on mitochondrial metabolism. It then should be investigated in clinical neuroprotection paradigms in neurodegenerative disease, particularly Parkinson’s disease.
The next step for amantadine involves investigations in neurons.
Antipsychotics
Risperidone needs more study to determine its neuroprotective potential. Its ability to reduce Complex I activity in regions of the brain, albeit not in the midbrain, indicates the need for further research as to its long-term safety in neurodegenerative diseases affecting the hippocampus, frontal lobe, and striatum, including Alzheimer’s disease, frontotemporal lobar degeneration, and Huntington’s disease. Clinical effects tend to contraindicate its use in Parkinson’s disease.
Although olanzapine should be better characterized as to its multiple neuroprotective effects (especially on the proteasome and mitochondrial permeability transition pore development), antimuscarinic and parkinsonian clinical properties argue against its application in Alzheimer’s disease and Parkinson’s disease.
Quetiapine should be better characterized as to its effects on αSyn, Aβ, tau, the proteasome, and protection against rotenone toxicity. Further studies using Aβ and initial studies using MPP+ should be carried out, with subsequent disease-modification studies in Alzheimer’s disease and Parkinson’s disease if the preceding studies indicate safety, although antihistaminic and anticholinergic clinical properties can constitute a limitation to use in Alzheimer’s disease.
Trifluoperazine, chlorpromazine, and thioridazine might be further studied in situations where inhibition of mitochondrial permeability transition pore development is of utility.
Aripiprazole and ziprasidone should be studied for their neuroprotective properties, given their low proclivities to induce extrapyramidal side effects in people with neurodegenerative disease.
Mood Stabilizers
Lithium should be studied for neuroprotection in patients with Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and cerebral ischemia. A clinical trial in Alzheimer’s disease is currently under way.
Investigation of valproate’s ability to induce mitochondrial permeability transition pore development but not mitochondrial membrane depolarization or cytochrome c release may yield information that may help develop neuroprotective mitochondrial strategies.
Valproate might be investigated in patients with Parkinson’s disease and oncological diseases for its antiapoptotic effects in the former and proapoptotic effects in microglia and the latter. Valproate’s ability to increase αSyn concentrations may be either beneficial or detrimental in Parkinson’s disease and other synucleinopathies, and further research is needed. Activated microglia appear to be of importance in neurodegenerative diseases, especially Alzheimer’s disease. Results of a recent clinical trial in Alzheimer’s disease are not yet available.
Antidepressants
Desipramine, nortriptyline, and maprotiline should be studied in other models of Huntington’s disease. If effective, they might be tried in other neurodegenerative disease models and in depressed patients with Huntington’s disease. Nortriptyline’s effects in Huntington’s disease yeast and amyotrophic lateral sclerosis mouse models deserve replication.
Fluoxetine has inhibited neural stem cell apoptosis, hippocampal apoptosis in newborn mice and rats and serotonin-induced apoptosis. Although it has some proapoptotic properties, fluoxetine should be studied further as a neuroprotectant in Alzheimer’s disease.
Paroxetine should be studied further for neuroprotective properties, especially in regard to reductions in Aβ and hyperphosphorylated tau.
Anxiolytics and Hypnotics
Buspirone has inhibited apoptosis in several neuronal models and now deserves study in regard to other related characteristics. If further studies indicate safety, studies in patients with neurodegenerative disease should then be undertaken.
Which types of GABA-A agonists protect against Aβ neurotoxicity and which do not requires clarification.
Clonazepam should be studied further for its restorative properties in Complex I deficiency, and should be better characterized in regard to apoptotic effects in neuronal models, especially on frontal lobe apoptosis in mature animals. If favorable results are forthcoming, it might then be tried in patients with neurodegenerative disease, especially Parkinson’s disease, although its association with falls in the elderly is a limitation.
Diphenhydramine should be further characterized in inflammatory, malignant, hypoxic, and other models where histamine plays a role.
Melatonin might now be investigated in patients with Alzheimer’s disease and in those with Parkinson’s disease.
Comprehensive Strategies
Deficiencies detailed in Table 5 deserve to be addressed in future studies. Validation of Table 6 translational predictive criteria awaits investigation. The relative predictive weightings of the various criteria also await outcome studies.
Combination therapies of psychotropics with differing profiles of neuroprotective actions may yield greater clinical impact than monotherapies. These varying profiles are depicted in Table 8. For example, across neurodegenerative diseases, the combination of lithium and melatonin might provide neuroprotective synergies, as might pramipexole, olanzapine, lithium, and nortriptyline in amyotrophic lateral sclerosis, lithium, and desipramine in Huntington’s disease, and pramipexole, lithium, desipramine, and melatonin in Alzheimer’s disease (Table 8). In Alzheimer’s disease, lithium and melatonin together might synergize efficacy at Aβ, hyperphosphorylated tau, reactive oxygen species, transition pore development, and apoptosis, with lithium perhaps improving ubiquitylation. In Parkinson’s disease, this combination plus pramipexole may synergize benefits to reactive oxygen species, transition pore, and apoptosis, with lithium perhaps improving ubiquitylation and pramipexole and melatonin perhaps synergizing efficacy on αSyn. It should be remembered, however, that some combination therapies, applied in cancer chemotherapy, have sometimes resulted in a reduced efficacy of all drugs and an increase in side-effects.28 Animal trials of proposed combinations would be a first step in evaluating their safety and efficacy.
Progress Thus Far: Clinical Trials
So far, some preliminary progress has been made in identifying the clinical neuroprotective properties of some of these agents. A search performed on October 9, 2007 using the search terms “randomized clinical trial AND (neuroprotection OR disease-modifying OR disease-modification OR disease modifying OR disease modification) for each drug revealed only one clinical neuroprotection study (ropinirole versus -dopa), and two studies evaluating glutathione reductase and a gamma interferon, relevant to disease progression, but without evaluating actual indices of clinical neuroprotection. A 6-18F-fluorodopa PET study of 186 patients with Parkinson’s disease randomized to either ropinirole or -dopa revealed a significant one third reduction in the rate of loss of dopamine terminals in subjects treated with ropinirole.29 A study of valproate plus placebo versus valproate plus melatonin in patients with epilepsy demonstrated a significant increase in glutathione reductase in the melatonin group, but no clinical indices of actual neuroprotection were evaluated in that study.30 A study in patients with relapsing-remitting multiple sclerosis identified a relationship between sertraline treatment of depression and attenuation of proinflammatory cytokine IFN-gamma, but again, actual indices of clinical neuroprotection were not assessed.31 In addition to the findings of the search, the CALM-Parkinson’s disease study involving the dopamine agonist pramipexole in Parkinson’s disease found faster progression (or at least less improvement on total UPDRS score) but slower dopamine transporter signal loss than with -dopa over 46 months,32 although the study has been criticized for lack of a placebo, group heterogeneity, and confounding influences on dopamine transporters. In contrast, a 2-year study of ropinirole found no significant difference in fluorodopa uptake compared to -dopa treatment (−13% versus −18%).33
A search of clinical trials (www.clinicaltrials.gov) on October 9, 2007 using the terms (neuroprotection OR disease-modifying OR disease-modification OR disease modifying OR disease modification) and neurodegenerative diseases revealed only a few studies in progress. These included pramipexole in amyotrophic lateral sclerosis, early versus delayed pramipexole in Parkinson’s disease, and valproate in spinal muscular atrophy. Since that time, as of February 1, 2009, additional studies have been registered. In Alzheimer’s disease, these include a short-term study of CSF tau epitopes with lithium, brain volume and clinical progression with valproate, and hippocampal volume, brain volume, and clinical progression with escitalopram. In frontotemporal dementia, there is a single study of CSF and brain volume with quetiapine versus D-amphetamine. In Huntington’s disease, there is a study of CSF BDNF levels with lithium versus valproate. In dementia with Lewy bodies and Parkinson’s disease dementia (PDD), there is a study of clinical progression with ramelteon. In Parkinson’s disease, there is a study of striatal dopamine transporter by β-CIT SPECT with pramipexole versus -dopa while an 8 year study of disability with pramipexole has been terminated. Only the spinal muscular atrophy and dementia with Lewy bodies/PDD studies employ clinical neuroprotective designs (delayed-start paradigm), and the validity of biomarker correlates, particularly dopamine transporter measures in Parkinson’s disease, continues to be studied.
The discussion above relies on multiple investigative approaches using a number of different psychotropics in a variety of models and a diversity of cell lines. A major caveat is that preclinical results do not necessarily translate into clinical realities. For example, favorable preclinical findings for the neuroprotectant minocycline exist in Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, stroke, spinal cord injury, and MS models, but a recent phase III trial in patients with amyotrophic lateral sclerosis was halted because of a 25% faster rate of neurological progression with the active drug than with placebo.34 Nevertheless, some generalizations seem possible at this stage. The considerations above are offered in hopes of stimulating the identification and development of pharmaceuticals that are useful both for symptomatic improvement and for long-term neuroprotection in neurodegenerative disease. Pursuit of the directions for research suggested above may contribute to that development.
Prof. Avram Hershko shared the 2004 Nobel Prize in Chemistry with Aaron Ciechanover and Irwin Rose for “for the discovery of ubiquitin-mediated protein degradation.” He is a research professor in the Department of Biochemistry at the Technion’s Rappaport Faculty of Medicine in Haifa.
Prof. Dan Shechtman – was awarded to Dan Shechtman “for the discovery of quasicrystals”.
Nobel Prize in Chemistry 2011
On Dec. 10, 2011 as Prof. Dan Shechtman received his Nobel prize in chemistry, hundreds of Technion students gathered in the Zielony Student Union to watch the ceremony live in the Heller Cinema. A standing ovation was given to Prof. Shechtman when he received the prize.
Daniel Shechtman is awarded the Nobel Prize for his discovery of quasicrystals. Discussed here by Professor Martyn Poliakoff and Sixty Symbols’ Professor Phil Moriarty.
Technion-Cornell Innovation Institute – Craig Gotsman Interview
Interview with Prof. Craig Gotsman, Technion Computer Science professor and Founding Director of TCII-Technion-Cornell Innovation Institute. This institute is a joint venture of the Technion and Cornell University, and will be a key component of the new Cornell NYC Tech campus, a unique high-tech graduate school to be established in New York City. The goal of the entire NYC Tech campus, and the TCII within it, as conceived by Mayor Bloomberg, is to turn NYC into the high-tech capital of the world. This will be achieved by developing TCII into a fertile breeding ground for high-tech engineers. Google, New York will be the interim home of the Technion-Cornell Innovation Institute (TCII) and the CornellNYC Tech Campus. Google will initially provide 22,000 square feet, expandable to 58,000 square feet – free of charge – until the completion of the Roosevelt Island campus in 2017.
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