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Archive for the ‘Diagnostic Immunology’ Category


Accelerating Clinical Next-Generation Sequencing: Navigating the Path to Reimbursement

Reporter: Aviva Lev-Ari, PhD, RN

Session at PMWC 2018 Silicon Valley

http://www.pmwcintl.com/sessionthemes-accelerating-clinical-next-generation-sequencing-2018sv/

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cell-free DNA (cfDNA) tests could become the ultimate “Molecular Stethoscope” that opens up a whole new way of practicing Medicine

 

Reporter: Aviva Lev-Ari, PhD, RN

The first commercial application of cfDNA sequencing debuted in 2011. New blood tests can identify Down’s syndrome and similar genetic conditions during the first months of pregnancy by checking the fetal DNA in the bloodstream of a pregnant woman. (Anywhere from 10 to 15 percent of the DNA in a pregnant woman’s blood comes from the placenta, which is genetically similar to the fetus.) These maternal blood tests are fast replacing less-accurate procedures, such as ultrasound plus blood analysis.

More recently, researchers have started looking at cfDNA to develop so-called liquid biopsies, which analyze a tumor’s genetic makeup or look for evidence of a cancer recurrence. Tumors often spill DNA into the blood as they grow and divide, and because they are usually riddled with mutations, their scrambled DNA is clearly different from that found in normal DNA fragments. The first liquid biopsy test was launched only three years ago; although they are not yet part of routine care, the field is growing quickly. One company says it will give liquid biopsy tests to one million people in the next five years, and another has raised nearly $1 billion for its studies.

A similar cfDNA method is being tested for newly transplanted organs, which are at risk of being rejected by the recipient’s immune system. Currently, transplant doctors check a transplanted organ’s health by performing repeated biopsies, which are expensive and invasive. After a transplant small amounts of donor DNA from the new heart or kidney, for example, circulate in the blood as part of the normal process of cell birth and death. If the host immune system attacks the foreign organ, the proportion of donor DNA increases as more and more foreign cells die. One company, CareDx, already sells a test that picks up on that change for people who have had kidney transplants.

The researchers invented a way to boost the signal by reducing human DNA in blood samples. Their spin-off company, Karius, launched a test earlier this year to identify bacteria, fungi, viruses or parasites in hospitalized patients. It can spot infections in organs that are too dangerous for biopsies, including the lung and the brain, Kertesz says—and it is most useful for people with mystery infections or who are too sick to endure a surgery.

cell-free DNA tests in the future include stroke, or autoimmune conditions such as lupus

 

SOURCE

One Test May Spot Cancer, Infections, Diabetes and More

Researchers are starting to diagnose more ailments using DNA fragments found in the blood

https://www.scientificamerican.com/article/one-test-may-spot-cancer-infections-diabetes-and-more/

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

During pregnancy, the baby is mostly protected from harmful microorganisms by the amniotic sac, but recent research suggests the baby could be exposed to small quantities of microbes from the placenta, amniotic fluid, umbilical cord blood and fetal membranes. One theory is that any possible prenatal exposure could ‘pre-seed’ the infant microbiome. In other words, to set the right conditions for the ‘main seeding event’ for founding the infant microbiome.

When a mother gives birth vaginally and if she breastfeeds, she passes on colonies of essential microbes to her baby. This continues a chain of maternal heritage that stretches through female ancestry for thousands of generations, if all have been vaginally born and breastfed. This means a child’s microbiome, that is the trillions of microorganisms that live on and in him or her, will resemble the microbiome of his/her mother, the grandmother, the great-grandmother and so on, if all have been vaginally born and breastfed.

As soon as the mother’s waters break, suddenly the baby is exposed to a wave of the mother’s vaginal microbes that wash over the baby in the birth canal. They coat the baby’s skin, and enter the baby’s eyes, ears, nose and some are swallowed to be sent down into the gut. More microbes form of the mother’s gut microbes join the colonization through contact with the mother’s faecal matter. Many more microbes come from every breath, from every touch including skin-to-skin contact with the mother and of course, from breastfeeding.

With formula feeding, the baby won’t receive the 700 species of microbes found in breast milk. Inside breast milk, there are special sugars called human milk oligosaccharides (HMO’s) that are indigestible by the baby. These sugars are designed to feed the mother’s microbes newly arrived in the baby’s gut. By multiplying quickly, the ‘good’ bacteria crowd out any potentially harmful pathogens. These ‘good’ bacteria help train the baby’s naive immune system, teaching it to identify what is to be tolerated and what is pathogen to be attacked. This leads to the optimal training of the infant immune system resulting in a child’s best possible lifelong health.

With C-section birth and formula feeding, the baby is not likely to acquire the full complement of the mother’s vaginal, gut and breast milk microbes. Therefore, the baby’s microbiome is not likely to closely resemble the mother’s microbiome. A baby born by C-section is likely to have a different microbiome from its mother, its grandmother, its great-grandmother and so on. C-section breaks the chain of maternal heritage and this break can never be restored.

The long term effect of an altered microbiome for a child’s lifelong health is still to be proven, but many studies link C-section with a significantly increased risk for developing asthma, Type 1 diabetes, celiac disease and obesity. Scientists might not yet have all the answers, but the picture that is forming is that C-section and formula feeding could be significantly impacting the health of the next generation. Through the transgenerational aspect to birth, it could even be impacting the health of future generations.

References:

https://blogs.scientificamerican.com/guest-blog/shortchanging-a-babys-microbiome/

https://www.ncbi.nlm.nih.gov/pubmed/23926244

https://www.ncbi.nlm.nih.gov/pubmed/26412384

https://www.ncbi.nlm.nih.gov/pubmed/25290507

https://www.ncbi.nlm.nih.gov/pubmed/25974306

https://www.ncbi.nlm.nih.gov/pubmed/24637604

https://www.ncbi.nlm.nih.gov/pubmed/22911969

https://www.ncbi.nlm.nih.gov/pubmed/25650398

https://www.ncbi.nlm.nih.gov/pubmed/27362264

https://www.ncbi.nlm.nih.gov/pubmed/27306663

http://www.mdpi.com/1099-4300/14/11/2036

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464665/

https://www.ncbi.nlm.nih.gov/pubmed/24848255

https://www.ncbi.nlm.nih.gov/pubmed/26412384

https://www.ncbi.nlm.nih.gov/pubmed/28112736

http://ndnr.com/gastrointestinal/the-infant-microbiome-how-environmental-maternal-factors-influence-its-development/

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Multiple copies of the alpha tryptase gene drive Tryptase elevations may contribute to symptoms of dizziness and lightheadedness, skin flushing and itching, gastrointestinal complaints, chronic pain, and bone and joint problems

 

Reporter: Aviva Lev-Ari, PhD, RN

 

Monday, October 17, 2016

NIH scientists uncover genetic explanation for frustrating syndrome

Previously unexplained symptoms found associated with multiple copies of a single gene.

Other studies have indicated that four to six percent of the general public has high tryptase levels. While not all of these people experience symptoms, many do, raising the possibility that this mildly prevalent trait in some cases drives the symptoms, although how it does so remains unclear.

“This work suggests that multiple alpha tryptase gene copies might underlie health issues that affect a substantial number of people,” said NIAID Director Anthony S. Fauci, M.D. “Identifying one genetic cause for high tryptase opens the door for us to develop strategies for diagnosing and treating people carrying this genetic change.”

Previously,NIH’s National Institute of Allergy and Infectious Diseases (NIAID) researchers had observed that a combination of chronic and sometimes debilitating symptoms, such as hives, irritable bowel syndrome and overly flexible joints, runs in some families and is associated with high tryptase levels. Many affected family members with high tryptase also reported symptoms consistent with disorders of autonomic nervous system function (dysautonomia), including postural orthostatic tachycardia syndrome (POTS), which is characterized by dizziness, faintness and an elevated heartbeat when standing up.

SOURCE

https://www.nih.gov/news-events/news-releases/nih-scientists-uncover-genetic-explanation-frustrating-syndrome

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Milestones in Physiology & Discoveries in Medicine and Genomics: Request for Book Review Writing on Amazon.com


physiology-cover-seriese-vol-3individualsaddlebrown-page2

Milestones in Physiology

Discoveries in Medicine, Genomics and Therapeutics

Patient-centric Perspective 

http://www.amazon.com/dp/B019VH97LU 

2015

 

 

Author, Curator and Editor

Larry H Bernstein, MD, FCAP

Chief Scientific Officer

Leaders in Pharmaceutical Business Intelligence

Larry.bernstein@gmail.com

Preface

Introduction 

Chapter 1: Evolution of the Foundation for Diagnostics and Pharmaceuticals Industries

1.1  Outline of Medical Discoveries between 1880 and 1980

1.2 The History of Infectious Diseases and Epidemiology in the late 19th and 20th Century

1.3 The Classification of Microbiota

1.4 Selected Contributions to Chemistry from 1880 to 1980

1.5 The Evolution of Clinical Chemistry in the 20th Century

1.6 Milestones in the Evolution of Diagnostics in the US HealthCare System: 1920s to Pre-Genomics

 

Chapter 2. The search for the evolution of function of proteins, enzymes and metal catalysts in life processes

2.1 The life and work of Allan Wilson
2.2  The  evolution of myoglobin and hemoglobin
2.3  More complexity in proteins evolution
2.4  Life on earth is traced to oxygen binding
2.5  The colors of life function
2.6  The colors of respiration and electron transport
2.7  Highlights of a green evolution

 

Chapter 3. Evolution of New Relationships in Neuroendocrine States
3.1 Pituitary endocrine axis
3.2 Thyroid function
3.3 Sex hormones
3.4 Adrenal Cortex
3.5 Pancreatic Islets
3.6 Parathyroids
3.7 Gastointestinal hormones
3.8 Endocrine action on midbrain
3.9 Neural activity regulating endocrine response

3.10 Genomic Promise for Neurodegenerative Diseases, Dementias, Autism Spectrum, Schizophrenia, and Serious Depression

 

Chapter 4.  Problems of the Circulation, Altitude, and Immunity

4.1 Innervation of Heart and Heart Rate
4.2 Action of hormones on the circulation
4.3 Allogeneic Transfusion Reactions
4.4 Graft-versus Host reaction
4.5 Unique problems of perinatal period
4.6. High altitude sickness
4.7 Deep water adaptation
4.8 Heart-Lung-and Kidney
4.9 Acute Lung Injury

4.10 Reconstruction of Life Processes requires both Genomics and Metabolomics to explain Phenotypes and Phylogenetics

 

Chapter 5. Problems of Diets and Lifestyle Changes

5.1 Anorexia nervosa
5.2 Voluntary and Involuntary S-insufficiency
5.3 Diarrheas – bacterial and nonbacterial
5.4 Gluten-free diets
5.5 Diet and cholesterol
5.6 Diet and Type 2 diabetes mellitus
5.7 Diet and exercise
5.8 Anxiety and quality of Life
5.9 Nutritional Supplements

 

Chapter 6. Advances in Genomics, Therapeutics and Pharmacogenomics

6.1 Natural Products Chemistry

6.2 The Challenge of Antimicrobial Resistance

6.3 Viruses, Vaccines and immunotherapy

6.4 Genomics and Metabolomics Advances in Cancer

6.5 Proteomics – Protein Interaction

6.6 Pharmacogenomics

6.7 Biomarker Guided Therapy

6.8 The Emergence of a Pharmaceutical Industry in the 20th Century: Diagnostics Industry and Drug Development in the Genomics Era: Mid 80s to Present

6.09 The Union of Biomarkers and Drug Development

6.10 Proteomics and Biomarker Discovery

6.11 Epigenomics and Companion Diagnostics

 

Chapter  7

Integration of Physiology, Genomics and Pharmacotherapy

7.1 Richard Lifton, MD, PhD of Yale University and Howard Hughes Medical Institute: Recipient of 2014 Breakthrough Prizes Awarded in Life Sciences for the Discovery of Genes and Biochemical Mechanisms that cause Hypertension

7.2 Calcium Cycling (ATPase Pump) in Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure: Contributions by Roger J. Hajjar, MD

7.3 Diagnostics and Biomarkers: Novel Genomics Industry Trends vs Present Market Conditions and Historical Scientific Leaders Memoirs

7.4 Synthetic Biology: On Advanced Genome Interpretation for Gene Variants and Pathways: What is the Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging

7.5 Diagnosing Diseases & Gene Therapy: Precision Genome Editing and Cost-effective microRNA Profiling

7.6 Imaging Biomarker for Arterial Stiffness: Pathways in Pharmacotherapy for Hypertension and Hypercholesterolemia Management

7.7 Neuroprotective Therapies: Pharmacogenomics vs Psychotropic drugs and Cholinesterase Inhibitors

7.8 Metabolite Identification Combining Genetic and Metabolic Information: Genetic association links unknown metabolites to functionally related genes

7.9 Preserved vs Reduced Ejection Fraction: Available and Needed Therapies

7.10 Biosimilars: Intellectual Property Creation and Protection by Pioneer and by

7.11 Demonstrate Biosimilarity: New FDA Biosimilar Guidelines

 

Chapter 7.  Biopharma Today

8.1 A Great University engaged in Drug Discovery: University of Pittsburgh

8.2 Introduction – The Evolution of Cancer Therapy and Cancer Research: How We Got Here?

8.3 Predicting Tumor Response, Progression, and Time to Recurrence

8.4 Targeting Untargetable Proto-Oncogenes

8.5 Innovation: Drug Discovery, Medical Devices and Digital Health

8.6 Cardiotoxicity and Cardiomyopathy Related to Drugs Adverse Effects

8.7 Nanotechnology and Ocular Drug Delivery: Part I

8.8 Transdermal drug delivery (TDD) system and nanotechnology: Part II

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

8.10 Natural Drug Target Discovery and Translational Medicine in Human Microbiome

8.11 From Genomics of Microorganisms to Translational Medicine

8.12 Confined Indolamine 2, 3 dioxygenase (IDO) Controls the Homeostasis of Immune Responses for Good and Bad

 

Chapter 9. BioPharma – Future Trends

9.1 Artificial Intelligence Versus the Scientist: Who Will Win?

9.2 The Vibrant Philly Biotech Scene: Focus on KannaLife Sciences and the Discipline and Potential of Pharmacognosy

9.3 The Vibrant Philly Biotech Scene: Focus on Computer-Aided Drug Design and Gfree Bio, LLC

9.4 Heroes in Medical Research: The Postdoctoral Fellow

9.5 NIH Considers Guidelines for CAR-T therapy: Report from Recombinant DNA Advisory Committee

9.6 1st Pitch Life Science- Philadelphia- What VCs Really Think of your Pitch

9.7 Multiple Lung Cancer Genomic Projects Suggest New Targets, Research Directions for Non-Small Cell Lung Cancer

9.8 Heroes in Medical Research: Green Fluorescent Protein and the Rough Road in Science

9.9 Issues in Personalized Medicine in Cancer: Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

9.10 The SCID Pig II: Researchers Develop Another SCID Pig, And Another Great Model For Cancer Research

Epilogue

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On its way for an IPO: mRNA platform, Moderna, Immune Oncology is recruiting 100 new Life Scientists in Cambridge, MA

Curator: Aviva Lev-Ari, PhD, RN

 

Deals:

Moderna has now raised $1.9 billion from investors like AstraZeneca – 9% stack [AstraZeneca’s Pascal Soriot helped get that all started with a whopping $240 million upfront in its 2013 deal, which was tied to $180 million in milestones.], with another $230 million on the table from grants. In addition to the financing announcement this morning, Moderna is also unveiling a pact to develop a new Zika vaccine, with BARDA putting up $8 million to get the program started while offering an option on $117 million more to get through a successful development program.

Novel Strategy in Biotech:

in biotech. Instead of grabbing one or two new drugs and setting out to gather proof-of-concept data to help establish its scientific credibility, the company has harvested a huge windfall of cash and built a large organization before even entering the clinic. And it did that without turning to an IPO.

Pipeline include:

  • The deal with AstraZeneca covers new drugs for cardiovascular, metabolic and renal diseases as well as cancer.
  • partners filed a European application to start a Phase I study of AZD8601, an investigational mRNA-based therapy that encodes for vascular endothelial growth factor-A (VEGF-A)
  • Moderna CEO spelled out plans to get the first 6 new drugs in the clinic by the end of 2016.
  • The first human study was arranged for the infectious disease drug mRNA 1440, which began an early stage study in 2015.
  • Moderna built up a range of big preclinical partnerships.
  • CEO Bancel says the number of drugs in development has swelled to 11, with the first set of data slated to be released in 2017.
  • Moderna also plans to add about 10 drugs to the clinic by next summer,

 

SOURCES

UPDATED: Booming Moderna is raising $600M while ramping up manufacturing and clinical studies

$1.9B in: Moderna blueprints $100M facility, plans to double the pipeline after a $474M megaround

http://endpts.com/moderna-blueprints-100m-facility-plans-to-double-the-pipeline-after-a-474m-megaround/?utm_source=Sailthru&utm_medium=email&utm_campaign=Issue:%202016-09-07%20BioPharma%20Dive%20%5Bissue:7155%5D&utm_term=BioPharma%20Dive

 

Moderna Therapeutics Deal with Merck: Are Personalized Vaccines here?

Curator & Reporter: Stephen J. Williams, PhD – August 11, 2016

https://pharmaceuticalintelligence.com/2016/08/11/moderna-therapeutics-deal-with-merck-are-personalized-vaccines-here/

 

at #JPM16 – Moderna Therapeutics turns away an extra $200 million: with AstraZeneca (collaboration) & with Merck ($100 million investment)

Reporter: Aviva Lev-Ari, PhD, RN – January 13, 2016

https://pharmaceuticalintelligence.com/2016/01/13/at-jpm16-moderna-therapeutics-turns-away-an-extra-200-million-with-astrazeneca-collaboration-with-merck-100-million-investment/

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Inotuzumab Ozogamicin: Success in relapsed/refractory Acute Lymphoblastic Leukemia (ALL)

Reporter: Aviva Lev-Ari, PhD, RN

 

About Inotuzumab Ozogamicin

Inotuzumab ozogamicin is an investigational antibody-drug conjugate (ADC) comprised of a monoclonal antibody (mAb) targeting CD22,9 a cell surface antigen expressed on approximately 90 percent of B-cell malignancies,10 linked to a cytotoxic agent. When inotuzumab ozogamicin binds to the CD22 antigen on malignant B-cells, it is internalized into the cell, where the cytotoxic agent calicheamicin is released to destroy the cell.11

Inotuzumab ozogamicin originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing, clinical development and commercialization activities for this molecule.

Acute lymphoblastic leukemia (ALL)

is an aggressive type of leukemia with high unmet need and a poor prognosis in adults.4The current standard treatment is intensive, long-term chemotherapy.5 In 2015, it is estimated that 6,250 cases of ALL will be diagnosed in the United States6, with about 1 in 3 cases in adults. Only approximately 20 to 40 percent of newly diagnosed adults with ALL are cured with current treatment regimens.7 For patients with relapsed or refractory adult ALL, the five-year overall survival rate is less than 10 percent.8

REFERENCES

1 Fielding A. et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood. 2006; 944-950.

2 U.S. Food and Drug Administration Safety and Innovation Act. Available at: http://www.gpo.gov/fdsys/pkg/PLAW-112publ144/pdf/PLAW-112publ144.pdf(link is external).Accessed July 11, 2015.

3 U.S. Food and Drug Administration Frequently Asked Questions: Breakthrough Therapies. Available at:http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/FDASIA/ucm341027.htm(link is external). Accessed July 11, 2015.

4 National Cancer Institute: Adult Acute Lymphoblastic Leukemia Treatment (PDQ®) – General Information About Adult Acute Lymphoblastic Leukemia (ALL). Available at:http://www.cancer.gov/cancertopics/pdq/treatment/adultALL/HealthProfessional/page1(link is external). Accessed July 11, 2015.

5 American Cancer Society: Typical treatment of acute lymphocytic leukemia. Available at:http://www.cancer.org/cancer/leukemia-acutelymphocyticallinadults/detailedguide/leukemia-acute-lymphocytic-treating-typical-treatment(link is external). Accessed July 11, 2015.

6 American Cancer Society: What are the key statistics about acute lymphocytic leukemia? Available at:http://www.cancer.org/cancer/leukemia-acutelymphocyticallinadults/detailedguide/leukemia-acute-lymphocytic-key-statistics(link is external). Accessed February 18, 2015.

7 Manal Basyouni A. et al. Prognostic significance of survivin and tumor necrosis factor-alpha in adult acute lymphoblastic leukemia. doi:10.1016/j.clinbiochem.2011.08.1147.

8 Fielding A. et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood. 2006; 944-950.

9 Clinicaltrials.gov. A Study of Inotuzumab Ozogamicin versus Investigator’s Choice of Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01564784?term=inotuzumab&rank=7(link is external). Accessed July 11, 2015.

10 Leonard J et al. Epratuzumab, a Humanized Anti-CD22 Antibody, in Aggressive Non-Hodgkin’s Lymphoma: a Phase I/II Clinical Trial Results. Clinical Cancer Research. 2004; 10: 5327-5334.

11 DiJoseph JF. Antitumor Efficacy of a Combination of CMC-544 (Inotuzumab Ozogamicin), a CD22-Targeted Cytotoxic Immunoconjugate of Calicheamicin, and Rituximab against Non-Hodgkin’s B-Cell Lymphoma. Clin Cancer Res. 2006; 12: 242-250.

SOURCE

http://www.pfizer.com/news/press-release/press-release-detail/pfizer_s_inotuzumab_ozogamicin_receives_fda_breakthrough_therapy_designation_for_acute_lymphoblastic_leukemia_all

Other related article Published on this Open Access Online Scientific Journal include the following:

STORY OF A LEUKEMIA FIGHTER

Nicole L. Gularte, MBA

https://pharmaceuticalintelligence.com/2016/08/21/cancer-the-future-immunotherapy/

https://pharmaceuticalintelligence.com/?s=Acute+Lymphoblastic+Leukemia+%28ALL%29+

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