Category Archives: Gene Medicine

Precision medicine is expanding into psychiatry, as new tests emerge to detect the underlying genetic or physiological causes of disorders in specific individuals and companion diagnostics are developed to guide the selection of therapeutics.

Depression affects approximately 17 million adults in the U.S. nearly 7% of the U.S. population, according to the National Institute of Mental Health. Yet, until quite recently, new treatment approaches were one-size-fits-all. Prozac (fluoxetine), a selective serotonin reuptake inhibitor (SSRI), is the poster child. Such treatments were developed for large populations of depressed individuals, but they dont work for everyone, Hans Eriksson,M.D., Ph.D., chief clinical development officer at HMNC Brain Health, told BioSpace.

As a clinical psychiatrist, I was struck by the fact that depressed patients have many different manifestations. Some may be sad, have low energy and eat and sleep a lot, while others with the same condition may be irritable, agitated, eat less and wake up early. It was a struggle to understand whether the same biology was at work. Until recently, we lacked tools (to do that), Eriksson said.

Now, he continued, with advances in genetic analyses and artificial intelligence, science is on the brink of developing psychiatry into a much more sophisticated scientific discipline. That implies the combination of novel and repurposed interventions with precision applications.

For example, about 30% of depressed patients seem to have a hyperactive stress response system that isnt controlled the normal way, Eriksson said. Some patients with chronic depression could, therefore, be treated with a vasopressin V1b antagonist to control the central overactivity in the brain that triggers the production of a stress hormone.

Scientists working with HMNC Brain Health have tested the hyperactive stress response in individuals and mapped it to genetics, which yielded a relevant set of single nucleotide polymorphisms (SNPs). Consequently, the company has the genetic signature of individuals with a tendency toward hyperactive stress response systems the V1b test.

HMNC Brain Health subsidiary, Nelivabon, is in-licensing a V1b antagonist (BH-200) that, with the companion V1b test, has the potential to improve outcomes by targeting the patient population best able to benefit from this intervention.

The V1b antagonist was in phase II trials at Sanofi a decade ago, and demonstrated efficacy, Eriksson said. Although it showed statistical significance, it would have competed with generics and was not developed further. Our belief is that its efficacy was driven by a subset of individuals with hyperactive stress systems. So, with the V1b test, we expect to see superior efficacy in this population.

Eriksson said that HMNC Brain Health is a pioneer in developing precision medicine for the psychiatric space. Its possible because of increasing knowledge in neuroscience, the availability of cost-effective genetics analysis and the increasing maturation of artificial intelligence.

AI has simplified things. We can do broad genetic analyses of populations and AI can help us find genetic signatures that may not be evident otherwise. Then we can test to verify that the findings are meaningful, he stated.

As more is learned about the brain, scientists are also exploring drugs with new mechanisms of action and modifications of drugs of abuse, such as psilocybin and ecstasy, to develop appropriate, controlled treatments.

Ketamine is a good example. It has been used as an anesthetic for more than 50 years and some researchers are showing that it also has an antidepressant effect. Unfortunately, in about a quarter of patients, its side-effects include dissociative experiences (such as hallucinations) and increased blood pressure when delivered intranasally or intravenously. Therefore, the approved formulation of esketamine has to be administered under the supervision of a healthcare professional. That, however, leads to logistical issues in practical medicine, Eriksson pointed out.

HMNC Brain Health subsidiary, Ketabon, is developing an oral, extended-release formulation without those side-effects as a treatment for chronic depression. It has slow uptake, so lowers the risks, he said, which suggests it may be able to be taken by patients at home. A phase II study comparing this extended-release formulation administered in combination with traditional antidepressants, versus antidepressants alone, is underway at the Psychiatric Hospital of the University of Zurich.

HMNC Brain Health and its subsidiaries and partners are developing other trials for a variety of companion diagnostics, with several in or about to enter the clinic. Its ABCB1 gene variant test, which guides the selection of antidepressants, is already on the market in France, Germany and Switzerland.

We are in an era where repurposed and novel interventions are coming into this (psychiatric) space. As a clinician, Eriksson said, its promising to see growing access to differentiated treatments with different mechanisms of action.

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Psychiatry on the Brink: Precision Medicine Finally Streamlines Therapeutic Selection - BioSpace

Treatment with SGT-001 Solid Biosciences gene therapy candidate forDuchenne muscular dystrophy (DMD) improves lung function, according to data from the first six patients enrolled in the ongoing IGNITE DMD clinical trial.

The improvements, seen one year after a single infusion of the SGT-001 gene therapy into the vein, included better percent predicted peak expiratory flow, called PEF% predicted a measure of how fast air can be exhaled from the lungs and forced expiratory volume in one second, or FEV1% predicted, a measure of the amount of air that can be forced out of the lungs in one second.

These data are being presented in a poster at theChild Neurology Society 50th Annual Meeting, by Oscar H. Mayer, MD, attending pulmonologist and director of the Pulmonary Function Laboratory at Childrens Hospital of Philadelphia. The meeting is being held in Boston Sept. 29 through Oct. 2.

The improvements in pulmonary function endpoints [goals] seen in the IGNITE DMD study, from baseline [study start] to one year are very promising, especially given that loss of pulmonary function leads to respiratory failure and ultimately death and, to varying degrees, impacts all patients living with Duchenne muscular dystrophy, Mayer said in a press release.

DMD is caused by mutations in theDMDgene, which provides instructions for making dystrophin, a protein found in muscles. Its absence or near-absence leads to weakness in the muscles, including those involved inbreathing. SGT-001 is designed to deliver a gene encoding a shorter yet functional dystrophin, called microdystrophin, to the body via a viral vector.

IGNITE DMD (NCT03368742) is a Phase 1/2 clinical trial that aims to test if SGT-001 is safe, well-tolerated, and effective in boys with DMD. A total of eight participants have been given SGT-001 to date.

The latest data were obtained from three patients given a low dose of 5E13 vector genomes (vg)/kg, three boys given the high dose of 2E14 vg/kg, and three untreated (control) patients.

PEF% predicted data were available for two of the participants given low-dose SGT-001, two given the high dose, and two controls. In those given SGT-001, improvements ranged from 2.5% to 38.5% at one year. In the control group, the two patients had declines of 1.1% and 18.2%.

For FEV1% predicted, data were available for two boys given low-dose SGT-001, the three patients given high-dose therapy, and the three controls. Among treated patients, improvements ranged from 2.8% to 15.5% at one year. All control patients had declines, ranging from 8.7% to 17%.

The ability to improve pulmonary function in these patients, especially during a period when the untreated control [group] and natural history data indicate functional decline, is evidence of the potentially meaningful clinical benefit of SGT-001, said Roxana Donisa Dreghici, senior vice president and head of clinical development at Solid.

Earlier this month, the company had announced positive 1.5-year data showing durable production of microdystrophin in muscles, while also supporting the previously reported benefits in functional abilities and patient-reported outcomes.

These data were presented at the World Muscle Society 2021 Virtual Congress, in an oral presentation titled IGNITE DMD Phase I/II ascending dose study of SGT-001 microdystrophin gene therapy for DMD: 1.5-year functional outcomes update, by Vamshi K. Rao, MD. Rao is an attending physician in neurology at Lurie Childrens Hospital, in Chicago, and assistant professor of pediatrics at the Northwestern University Feinberg School of Medicine.

These data provide encouraging evidence of functional benefit at 1.5 years post-treatment compared with natural history data and show meaningful improvement in patient-reported outcomes, Rao said.

The 1.5-year data also showed improved lung function. Specifically, the mean improvement in percent predicted forced vital capacity the total amount of air exhaled during the FEV test from the studys start for the three patients given high-dose SGT-001 was 8.5%, and the mean improvement compared with controls was 16% over the same time period.

To our knowledge, Solid is the first company to report improvement in multiple assessments of pulmonary function following administration of a Duchenne gene therapy, said Ilan Ganot,CEO,president,andco-founder of Solid.

These data add to the data we have previously reported from the IGNITE DMD clinical trial, Ganot said. We believe that exploring diverse endpoints will enable us to better understand the totality of the potential benefits that SGT-001 may provide across the spectrum of Duchenne-related disease manifestations.

Mayer said he is looking forward to further pulmonary function data and analysis from IGNITE DMD, saying such results should provide additional insight into the potential benefit that SGT-001 may provide for patients with Duchenne.

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DMD Gene Therapy SGT-001 Improves Lung Function in Boys in Trial - Muscular Dystrophy News

SOUTHLAKE, Texas, September 30, 2021--(BUSINESS WIRE)--OncoNano Medicine, Inc. today announced a poster presentation at The American Association for Cancer Research (AACR) Virtual Conference on Tumor Immunology and Immunotherapy to be held on October 5-6, 2021.

Full details of the presentation are listed below:

TITLE: ONM-501 A Synthetic Polyvalent STING Agonist for Cancer Immunotherapy

PRESENTER: Qintai Su, Ph.D.DATE: October 5-6, 2021LOCATION: Virtual

The development of ONM-501 represents a new concept in STING activation that could overcome the challenges observed with earlier STING agonists. ONM-501 encapsulates the endogenous STING agonist cGAMP with a proprietary micelle that induces polyvalent STING condensation and prolongs innate immune activation to offer dual burst and sustained STING activation for a potential highly effective immunotherapy against cancer.

About OncoNano Medicine

OncoNano Medicine is developing a new class of products that utilize principles of molecular cooperativity in their design to exploit pH as a biomarker to diagnose and treat cancer with high specificity. Our product candidates and interventions are designed to help patients across the continuum of cancer care and include solid tumor therapeutics, agents for real-time image-guided surgery and a platform of immune-oncology therapeutics that activate and guide the bodys immune system to target cancer.

OncoNanos lead development candidate is pegsitacianine, a novel fluorescent nanoprobe, that is currently under study in Phase 2 clinical trials as a real-time surgical imaging agent for use in multiple cancer surgeries. ONM-501, OncoNanos second development program, is a next generation STING (STimulator of INterferon Genes) agonist that is advancing towards a first in human trial in the first half of 2023. Pegsitacianine and ONM-501 have been supported by grants received from the Cancer Prevention Research Institute of Texas. Learn more at http://www.OncoNano.com.

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View source version on businesswire.com: https://www.businesswire.com/news/home/20210930005048/en/

Contacts

MacDougallLauren Arnold781-235-3060larnold@macbiocom.com

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OncoNano Medicine to Present at The American Association for Cancer Research Virtual Conference on Tumor Immunology and Immunotherapy - Yahoo Finance

image:We know of hundreds of gene variants that are more likely to show up in individuals suffering obesity and other diseases. But more likely to show up does not mean causing the disease. This uncertainty is a major barrier to exploit the power of population genomics to identify targets to treat or cure obesity. To overcome this barrier, we developed an automated pipeline to simultaneously test hundreds of genes for a causal role in obesity. Our first round of experiments uncovered more than a dozen genes that cause and three genes that prevent obesity, said Eyleen ORourke of UVAs College of Arts & Sciences, the School of Medicines Department of Cell Biology and the Robert M. Berne Cardiovascular Research Center. We anticipate that our approach and the new genes we uncovered will accelerate the development of treatments to reduce the burden of obesity. view more

Credit: Dan Addison | UVA Communications

Promising news in the effort to develop drugs to treat obesity: University of Virginia scientists have identified 14 genes that can cause and three that can prevent weight gain. The findings pave the way for treatments to combat a health problem that affects more than 40% of American adults.

We know of hundreds of gene variants that are more likely to show up in individuals suffering obesity and other diseases. But more likely to show up does not mean causing the disease. This uncertainty is a major barrier to exploit the power of population genomics to identify targets to treat or cure obesity. To overcome this barrier, we developed an automated pipeline to simultaneously test hundreds of genes for a causal role in obesity. Our first round of experiments uncovered more than a dozen genes that cause and three genes that prevent obesity, said Eyleen ORourke of UVAs College of Arts & Sciences, the School of Medicines Department of Cell Biology and the Robert M. Berne Cardiovascular Research Center. We anticipate that our approach and the new genes we uncovered will accelerate the development of treatments to reduce the burden of obesity.

ORourkes new research helps shed light on the complex intersections of obesity, diet and our DNA. Obesity has become an epidemic, driven in large part by high-calorie diets laden with sugar and high-fructose corn syrup. Increasingly sedentary lifestyles play a big part as well. But our genes play an important role too, regulating fat storage and affecting how well our bodies burn food as fuel. So if we can identify the genes that convert excessive food into fat, we could seek to inactivate them with drugs and uncouple excessive eating from obesity.

Genomicists have identified hundreds of genes associated with obesity meaning the genes are more or less prevalent in people who are obese than in people with healthy weight. The challenge is determining which genes play causal roles by directly promoting or helping prevent weight gain. To sort wheat from chaff, ORourke and her team turned to humble worms known asC. elegans. These tiny worms like to live in rotting vegetation and enjoy feasting on microbes. However, they share more than 70% of our genes, and, like people, they become obese if they are fed excessive amounts of sugar.

The worms have produced great benefits for science. Theyve been used to decipher how common drugs, including the antidepressant Prozac and the glucose-stabilizing metformin, work. Even more impressively, in the last 20 years three Nobel prizes were awarded for the discovery of cellular processes first observed in worms but then found to be critical to diseases such as cancer and neurodegeneration. Theyve also been fundamental to the development of therapeutics based on RNA technology.

In new work just published in the scientific journal PLOS Genetics, ORourke and her collaborators used the worms to screen 293 genes associated with obesity in people, with the goal of defining which of the genes were actually causing or preventing obesity. They did this by developing a worm model of obesity, feeding some a regular diet and some a high-fructose diet.

This obesity model, coupled to automation and supervised machine learning-assisted testing, allowed them to identify 14 genes that cause obesity and three that help prevent it. Enticingly, they found that blocking the action of the three genes that prevented the worms from becoming obese also led to them living longer and having better neuro-locomotory function. Those are exactly the type of benefits drug developers would hope to obtain from anti-obesity medicines.

More work needs to be done, of course. But the researchers say the indicators are encouraging. For example, blocking the effect of one of the genes in lab mice prevented weight gain, improved insulin sensitivity and lowered blood sugar levels. These results (plus the fact that the genes under study were chosen because they were associated with obesity in humans) bode well that the results will hold true in people as well, the researchers say.

Anti-obesity therapies are urgently needed to reduce the burden of obesity in patients and the healthcare system, ORourke said. Our combination of human genomics with causality tests in model animals promises yielding anti-obesity targets more likely to succeed in clinical trials because of their anticipated increased efficacy and reduced side effects.

###

The researchers havepublished their findings in the scientific journal PLOS Genetics. The research team consisted of Wenfan Ke, Jordan N. Reed, Chenyu Yang, Noel Higgason, Leila Rayyan, Carolina Whlby, Anne E. Carpenter, Mete Civelek and ORourke.

The research was supported by the National Institutes of Health, grants DK118287, GM122547, DK087928, T32 HL007284 and GM122547; a Pew Charitable Trusts Biomedical Scholars Award; the W.M. Keck Foundation; and a Jeffress Trust Award.

To keep up with the latest medical research news from UVA, subscribe to theMaking of Medicineblog at http://makingofmedicine.virginia.edu.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Scientists discover 14 genes that cause obesity - EurekAlert

Jonathan Berg, MD, PhD, at the UNC School of Medicine, is a principal investigator of The Clinical Genome Resource, a multi-institution consortium initially launched in 2013 by the National Human Genome Research Institute to provide evidence-based evaluations of clinically relevant genes and variants.

CHAPEL HILL, NC Doctors have accurate diagnostic tests for some single-gene conditions, such as sickle cell disease or cystic fibrosis. But when it comes to understanding the genetic variants underlying most rare genetic conditions, there is still much to learn. This is where the Clinical Genome Resource Consortium (ClinGen) comes in.

This week, the NIH renewed three awards totaling $73.2 million over five years to continue building the Clinical Genome Resource, an effort to collect and archive information about clinically relevant genes and genomic variants alterations in the DNA sequence of a particular gene for use in precision medicine.

The ClinGen team at UNC-Chapel Hill, led by Jonathan Berg, MD, PhD, Bryson Distinguished Professor of Genetics and Medicine, was awarded a $24-million, five-year grant to scale biocuration and expert evaluation of genes and variants. The grant includes key contributors at the American College of Medical Genetics and Genomics (ACMG), ARUP Laboratories, Baylor College of Medicine, Georgetown University, Kaiser Foundation Research Institute (KFRI), Massachusetts Eye and Ear Infirmary, Mayo Clinic, the University of Miami, and RTI International.

This UNC-led project is part of a consortium including two other major programs: one spearheaded by the Broad Institute at MIT and Harvard and Geisinger, and a second led by Baylor College of Medicine and Stanford University.Read more from the NIH here.

Optimal clinical care depends on accurate information about the causes, natural history, and management of diseases, said Berg, director of the Program in Precision Medicine in Healthcare at the UNC School of Medicine (PPMH). With genomic analysis becoming more routine for patients suspected to have rare genetic conditions, the public availability of well-curated and expert knowledge about genes and variants is critical. Our goal is for ClinGen to provide a readily accessible and trusted resource that can be used by diagnostic laboratories, providers, and patients.

Over the next five years, ClinGen investigators, with the help of physician and patient stakeholders, will fill this important gap in care through the collection and evaluation of structured evidence on genetic conditions and the variants that cause them. The researchers will utilize frameworks developed during the initial phases of ClinGen to evaluate gene-disease relationships, classify genetic variants, and assess clinical actionability of genetic conditions; all results are made freely available online. Notably, ClinGen obtained FDA recognition for the methods used by its expert panels that classify genetic variants.

The core of the expert curation work is being conducted by diverse, international teams of clinical experts, basic scientists, clinical molecular geneticists, genetic counselors, biocurators and project coordinators. As part of our project, we intend to utilize the truly remarkable network of ClinGen contributors to conduct stakeholder engagement in multiple clinical domains, to improve the quality and impact of the resource and respond to the specific needs of each specialty, Berg said. UNCs project emphasizes the critical importance of data sharing, stakeholder engagement, assessment of physician and patient needs, and sustainability of the resource. The project also will focus on diversity of data sources, people, and organizations involved in generating the resource.

Investigators at RTI and KFRI are leading ClinGens efforts to assess clinical actionability utilizing a structured literature review and evaluation process developed in the early phases of ClinGen for both adult and pediatric conditions. The results of this work are already informing practice guidelines such as the ACMG recommendations for reporting of secondary findings in clinical exome and genome sequencing. In the current funding period, the team will develop a methodological framework for examining actionability of polygenic risk scores that are now being developed for common multifactorial conditions.

The ClinGen resource has had a broad impact in the genomics community and patient care, as demonstrated by use in professional guidelines and achievement of FDA recognition. The exceptional participation of more than 1,500 clinicians and scientists worldwide, many of whom are volunteers, reflects how the genomics community has embraced the ClinGen expert curation processes. ClinGens well-structured evidence-based assertions about clinically relevant genes and variants represents a body of genomic knowledge that is essential to reduce inconsistency in clinical practice and to facilitate the widespread application of genomic technologies to improve health.

The mission of Program in Precision Medicine in Healthcare at the UNC School of Medicine, funded by UNC Health system, is to use genomics and other technologies to advance precision medicine approaches to screening, prevention, diagnosis, and health management for North Carolinians in the UNC Health system and beyond. This Clinical Genome Resource grant will accelerate these endeavors and will significantly improve patient care.

UNC School of Medicine contact: Mark Derewicz, 919-923-0959

See the original post here:
UNC Awarded $24-million NIH Grant to Improve Genomic, Precision Medicine | Newsroom - UNC Health and UNC School of Medicine

CHAPEL HILL Doctors have accurate diagnostic tests for some single-gene conditions, such as sickle cell disease or cystic fibrosis. But when it comes to understanding the genetic variants underlying most rare genetic conditions, there is still much to learn. This is where the Clinical Genome Resource Consortium (ClinGen) comes in.

This week, theNIH renewed three awardstotaling $73.2 million over five years to continue building the Clinical Genome Resource, an effort to collect and archive information about clinically relevant genes and genomic variants alterations in the DNA sequence of a particular gene for use in precision medicine.

The ClinGen team at UNC-Chapel Hill, led byJonathan Berg, MD, PhD, Bryson Distinguished Professor of Genetics and Medicine, was awarded a $24-million, five-year grant to scale biocuration and expert evaluation of genes and variants. The grant includes key contributors at the American College of Medical Genetics and Genomics (ACMG), ARUP Laboratories, Baylor College of Medicine, Georgetown University, Kaiser Foundation Research Institute (KFRI), Massachusetts Eye and Ear Infirmary, Mayo Clinic, the University of Miami, and RTI International.

Jonathan Berg (UNC-CH photo)

This UNC-led project is part of a consortium including two other major programs: one spearheaded by the Broad Institute at MIT and Harvard and Geisinger, and a second led by Baylor College of Medicine and Stanford University.Read more from the NIH here.

Optimal clinical care depends on accurate information about the causes, natural history, and management of diseases, said Berg, director of the Program in Precision Medicine in Healthcare at the UNC School of Medicine (PPMH). With genomic analysis becoming more routine for patients suspected to have rare genetic conditions, the public availability of well-curated and expert knowledge about genes and variants is critical. Our goal is for ClinGen to provide a readily accessible and trusted resource that can be used by diagnostic laboratories, providers, and patients.

Over the next five years, ClinGen investigators, with the help of physician and patient stakeholders, will fill this important gap in care through the collection and evaluation of structured evidence on genetic conditions and the variants that cause them. The researchers will utilize frameworks developed during the initial phases of ClinGen to evaluate gene-disease relationships, classify genetic variants, and assess clinical actionability of genetic conditions; all results are made freely available online. Notably, ClinGen obtained FDA recognition for the methods used by its expert panels that classify genetic variants.

The core of the expert curation work is being conducted by diverse, international teams of clinical experts, basic scientists, clinical molecular geneticists, genetic counselors, biocurators and project coordinators. As part of our project, we intend to utilize the truly remarkable network of ClinGen contributors to conduct stakeholder engagement in multiple clinical domains, to improve the quality and impact of the resource and respond to the specific needs of each specialty, Berg said. UNCs project emphasizes the critical importance of data sharing, stakeholder engagement, assessment of physician and patient needs, and sustainability of the resource. The project also will focus on diversity of data sources, people, and organizations involved in generating the resource.

Investigators at RTI and KFRI are leading ClinGens efforts to assess clinical actionability utilizing a structured literature review and evaluation process developed in the early phases of ClinGen for both adult and pediatric conditions. The results of this work are already informing practice guidelines such as the ACMG recommendations for reporting of secondary findings in clinical exome and genome sequencing. In the current funding period, the team will develop a methodological framework for examining actionability of polygenic risk scores that are now being developed for common multifactorial conditions.

The ClinGen resource has had a broad impact in the genomics community and patient care, as demonstrated by use in professional guidelines and achievement of FDA recognition. The exceptional participation of more than 1,500 clinicians and scientists worldwide, many of whom are volunteers, reflects how the genomics community has embraced the ClinGen expert curation processes. ClinGens well-structured evidence-based assertions about clinically relevant genes and variants represents a body of genomic knowledge that is essential to reduce inconsistency in clinical practice and to facilitate the widespread application of genomic technologies to improve health.

(C) UNC

Originally posted here:
UNC lands $24M grant to drive more genetic research for precision medicine - WRAL Tech Wire

Credit: Scientific American Health & Medicine, Vol. 3, Issue No. 5 Advertisement

Medicine accomplished a huge feat at the start of 2020, when researchers produced the first mRNA vaccine to protect humans from SARS-CoV-2 infection. It was certainly not new technologythe vaccine platform had been under development for more than a decade and tested against multiple diseases, from flu to rabies. It represents our rapidly advancing understanding of how the body manufactures proteins, the molecules that are coded for by our genes. The potential to manipulate the very blueprints that our cells use to build the molecules and cells at the heart of disease is undoubtedly a game changer. Beyond vaccines, researchers have been devising treatments for cancer, lymphoma, AIDS, cystic fibrosis, and more, aided by new gene-editing technology, as physician Carolyn Barber (see How Designer DNA Is Changing Medicine) profiles in this collection. The next generation of lifesaving treatments may be manufactured right in our own bodies.

Such genetic advancements are being hyped as a way for prospective parents to screen their embryos for future diseasesbut the technology might not be ready for primetime, as genetic counselor Laura Hercher writes (see A New Era of Designer Babies May Be Based on Overhyped Science). And as always we have updates on the latest COVID newsfrom breakthrough infections (see Breakthrough Infections Do Not Mean COVID Vaccines Are Failing) to a surprising COVID risk (see People with COVID Often Infect Their Pets). Heres to your health, now and in the future!

This article was originally published with the title "The Blueprints of Health" in SA Health & Medicine 3, 5, (October 2021)

Andrea Gawrylewski is the collections editor at Scientific American.

Follow Andrea Gawrylewski on Twitter

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LEBANON, NH Patients with abnormal variants (mutations) in the DPYD gene are known to be at risk for severe toxicity from treatment with 5-fluorouracil or capecitabinechemotherapies commonly used to treat colorectal cancer, as well as pancreatic, breast, gastroesophageal and other cancers. But previous studies have not reported the extent to which these DPYD gene variants are linked to fatal chemotherapy toxicity, as fatal toxicity is rare in any individual study. Pooling studies is needed to examine the association of DPYD gene variants with this severe outcome.

In a meta-analysis of previously published studies, researchers at Dartmouths and Dartmouth-Hitchcocks Norris Cotton Cancer Center (NCCC), led by Gabriel A. Brooks, MD, MPH, found that uncommon variants in the DPYD gene, present in 4% of all cancer patients, were associated with a 25-times increased risk of fatal toxicity after treatment with standard doses of either chemotherapy drug. The absolute risk of fatal toxicity was 0.1% in patients without DPYD gene variants, and as high as 3.7% in patients with any of the three most severe DPYD gene variants.

The teams study, Pathogenic DPYD variants and treatment-related mortality in patients receiving fluoropyrimidine chemotherapy: A systematic review and meta-analysis, is newly published online in The Oncologist.

Though DPYD and other gene testing has been recommended by the European Medicines Agency since spring of 2020, gene testing is not widely done in the US before patients are administered chemotherapy with 5-fluorouracil or capecitabine. Brooks study suggests that adding pre-treatment screening may help prevent avoidable chemotherapy-related deaths without interrupting standard of care, as most patients who carry abnormal gene variants can still be treated with reduced doses of these chemotherapies. NCCC has already implemented routine screening for DPYD gene variants in most gastrointestinal cancer patients.

US organizations such as the Food & Drug Administration (FDA), the American Society of Clinical Oncology, or the National Comprehensive Cancer Network should consider recommending this testing. The FDA is currently considering a citizens petition advocating for more widespread genetic testing, of which I am a cosigner, says Brooks.

* * *

Gabriel A. Brooks, MD, MPH, is a medical oncologist in the Gastrointestinal Oncology Program and member of the Cancer Population Sciences Research Program at Dartmouths and Dartmouth-Hitchcocks Norris Cotton Cancer Center, and assistant professor of medicine at the Geisel School of Medicine at Dartmouth. His research focuses on systematic approaches to improving the delivery of safe and effective cancer care, with an emphasis on gastrointestinal cancers. @gabe_a_brooks

* * *

About Norris Cotton Cancer CenterNorris Cotton Cancer Center, located on the campus of Dartmouth-Hitchcock Medical Center (DHMC) in Lebanon, NH, combines advanced cancer research at Dartmouth Colleges Geisel School of Medicine in Hanover, NH with the highest level of high-quality, innovative, personalized, and compassionate patient-centered cancer care at DHMC, as well as at regional, multi-disciplinary locations and partner hospitals throughout NH and VT. NCCC is one of only 51 centers nationwide to earn the National Cancer Institutes prestigious Comprehensive Cancer Center designation, the result of an outstanding collaboration between DHMC, New Hampshires only academic medical center, and Dartmouth College. Now entering its fifth decade, NCCC remains committed to excellence, outreach and education, and strives to prevent and cure cancer, enhance survivorship and to promote cancer health equity through its pioneering interdisciplinary research. Each year the NCCC schedules 61,000 appointments seeing nearly 4,000 newly diagnosed patients, and currently offers its patients more than 100 active clinical trials.

About the Geisel School of MedicineFounded in 1797, the Geisel School of Medicine at Dartmouth strives to improve the lives of the communities it serves through excellence in learning, discovery, and healing. The Geisel School of Medicine is renowned for its leadership in medical education, healthcare policy and delivery science, biomedical research, global health, and in creating innovations that improve lives worldwide. As one of Americas leading medical schools, Dartmouths Geisel School of Medicine is committed to training new generations of diverse leaders who will help solve our most vexing challenges in healthcare.

About Dartmouth-Hitchcock HealthDartmouth-Hitchcock Health (D-HH), New Hampshires only academic health system and the states largest private employer, serves a population of 1.9 million across northern New England. D-H provides access to more than 2,000 providers in almost every area of medicine, delivering care at its flagship hospital, Dartmouth-Hitchcock Medical Center (DHMC) in Lebanon, NH. DHMC was named again in 2020 as the #1 hospital in New Hampshire by U.S. News & World Report, and recognized for high performance in 9 clinical specialties and procedures. Dartmouth-Hitchcock also includes the Norris Cotton Cancer Center, one of only 51 NCI-designated Comprehensive Cancer Centers in the nation; the Children's Hospital at Dartmouth-Hitchcock, the states only childrens hospital; affiliated member hospitals in Lebanon, Keene, and New London, NH, and Windsor, VT, and Visiting Nurse and Hospice for Vermont and New Hampshire; and 24 Dartmouth-Hitchcock clinics that provide ambulatory services across New Hampshire and Vermont. The D-H system trains nearly 400 residents and fellows annually, and performs world-class research, in partnership with the Geisel School of Medicine at Dartmouth and the White River Junction VA Medical Center in White River Junction, VT.

Meta-analysis

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Pathogenic DPYD variants and treatment-related mortality in patients receiving fluoropyrimidine chemotherapy: A systematic review and meta-analysis

10-Sep-2021

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Rare gene mutations lead to greatly increased risk of fatal chemotherapy toxicity - EurekAlert

ZURICH-SCHLIEREN, Switzerland and LAGUNA HILLS, Calif., Sept. 23, 2021 /PRNewswire/ -- DiNAQOR, a genetic medicine platform company focused on addressing severe inherited cardiac diseases, today announced it has expanded its leadership team by appointing veteran medical device leader Mark Dehdashtian to serve as Executive Vice President, Medical Devices.

Mark Dehdashtian, EVP, Medical Devices, DiNAQOR

As the company grows its U.S. footprint, Mr. Dehdashtian will oversee DiNAQOR's newly formed medical device division including its new manufacturing facility based in Laguna Hills, Calif. He will be responsible for the design, development, and production of genetic medicine delivery devices for the Company's localized, catheter-based multi-organ access platform.

"Mark brings to DiNAQOR the expertise that comes from 30 years of developing innovative medical devices that change patients' lives, and bringing them to market," said Johannes Holzmeister, M.D., Chairman and CEO of DiNAQOR. "We are thrilled to have a real leader in this area take on this important role, especially at such an exciting time for our company."

Mr. Dehdashtian led a distinguished 25-year career at Edwards Lifesciences, where he served in several senior-level positions, including Vice President of Research and Development for the Heart Valve Therapy, Advanced Technology and Cardiac Surgery Systems divisions. At Edwards, Mr. Dehdashtian designed the delivery systems for transcatheter heart valves and was instrumental in commercializing the transcatheter heart valve transapical systems. He holds more than 60 U.S. patents as well as many international patents, most notably for the design of the transcatheter heart valve, and his work has been published in several peer-reviewed journals. Mr. Dehdashtian has served as a member of medical technology steering committees to develop industry-wide standards.

"My career has been devoted to developing and bringing game-changing technologies to patients," commented Mr. Dehdashtian. "DiNAQOR's organ access platform is a real innovation in administering genetic medicines, and gene therapies in particular, that can improve the standard of care for patients. I'm excited to be a part of this, and to help DiNAQOR grow its U.S. presence."

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DiNAQOR's localized, catheter-based organ access platform enables gene therapies to be routed directly to the cardiac muscle, maximizing biodistribution and transduction of the cardiac cells. This new minimally invasive approach, which is actively being used in several pre-clinical studies, may minimize potential adverse effects of systemic gene therapy delivery while lowering the total dose of vectors and thus the cost. DiNAQOR is also developing the platform for other organs.

"A device-based approach to gene therapy holds the promise of minimizing exposure to the viral vector, thereby enhancing both the safety and efficacy of our therapy," said Valeria Ricotti, M.D., Chief Medical Officer of DiNAQOR. "Our aim is to treat a broader population of patients while avoiding the kind of systemic side effects that have caused a number of clinical programs to be put on hold."

About DiNAQOR

DiNAQOR is a genetic medicine platform company focused on advancing novel solutions for patients suffering from severe, inherited forms of heart disease. The company is headquartered in Zurich-Schlieren, Switzerland, with additional presence in London, England; Hamburg, Germany; Laguna Hills, California; and Boston, Massachusetts. For more information visit http://www.dinaqor.com.

Contact

KWM CommunicationsKellie Walsh914-315-6072kwalsh@kwmcommunications.com

DiNAQOR logo (PRNewsfoto/DiNAQOR)

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DiNAQOR Appoints Medical Device Leader Mark Dehdashtian to Oversee New U.S.-Based Division, Device Development and Production - Yahoo Finance

NEW YORK and RESEARCH TRIANGLE PARK, N.C., Sept. 23, 2021 (GLOBE NEWSWIRE) -- Sio Gene Therapies Inc. (NASDAQ: SIOX), a clinical-stage company focused on developing gene therapies to radically improve the lives of patients with neurodegenerative diseases, announced today that the company will participate in select upcoming investor and scientific conferences. Details can be found below.

Cantor Fitzgerald Global Healthcare Conference

Chardan Genetic Medicines Conference

Alliance for Regenerative Medicine: Cell & Gene Meeting on the Mesa

About Sio Gene TherapiesSio Gene Therapies combines cutting-edge science with bold imagination to develop genetic medicines that aim to radically improve the lives of patients. Our current pipeline of clinical-stage candidates includes the first potentially curative AAV-based gene therapies for GM1 gangliosidosis and Tay-Sachs/Sandhoff diseases, which are rare and uniformly fatal pediatric conditions caused by single gene deficiencies. We are also expanding the reach of gene therapy to highly prevalent conditions such as Parkinsons disease, which affects millions of patients globally. Led by an experienced team of gene therapy development experts, and supported by collaborations with premier academic, industry and patient advocacy organizations, Sio is focused on accelerating its candidates through clinical trials to liberate patients with debilitating diseases through the transformational power of gene therapies. For more information, visit http://www.siogtx.com.

Contacts:

Media Josephine Belluardo, Ph.D. LifeSci Communications(646) 751-4361jo@lifescicomms.cominfo@siogtx.com

Investors and AnalystsParag V. MeswaniSio Gene Therapies Inc.Chief Commercial Officerinvestors@siogtx.com

Link:
Sio Gene Therapies to Participate in Upcoming Conferences - GlobeNewswire