Daily Archives: October 3, 2021

Genetic Technologies (GENE) today announced a collaboration with the Institute of Public Health in St Louis USA to expand the predictive capabilities of the companys GeneType for Breast Cancer product for women of African descent. GENE is a genomics and AI-driven preventative health business.

In a press release, the company says this is, In line with the strategic objective to invest to expand testing to provide inclusive polygenic risk scores for multi-ethnic populations.

Its known that significant unmet need exists for polygenic risk testing for ethnically diverse populations. Risks of mortality from breast cancer is estimated to be 40% higher in African American women than Caucasian women, but most polygenic scores are calculated based on populations that are mainly Northern European. There are more than 47 million individuals of African descent in the US. The lifetime probability of developing non-hereditary breast cancer is 11.5% (1 in 9) for this population.

The self-funded collaborative study will support expanded risk testing for populations of African descent. It is designed to enable identification of high-risk individuals who could benefit from advanced testing.

The study will be in collaboration with Professor Graham Colditz, a world-renowned epidemiologist. From 1999 to 2006 Colditz was Principal Investigator of the ongoing Nurses Health Study located at the Brigham and Womens Hospital. He now specializes in risk modeling for breast cancer in women of African American descent.

Polygenic risk models are required to be validated for use with multiple ethnicities and therefore GENE will be validating samples that have both genotype data and the relevant clinical information to cover this expanded population.

The collaboration is anticipated to require around 9 months of research and processing at GENEs Melbourne Laboratory.

Commenting on the study, CEO Simon Morriss said: Expanding our capabilities to include those of African descent is a critical element of our long-term strategy. To fully address the growing burden of common complex diseases on our healthcare systems we need to be able to provide predictive risk tests for all individuals to empower them with the information to proactively manage their health and understand their risk. This is the first step in our response to address the unmet demand for tests that have been validated on multi population datasets. We will continue to assess our product portfolio to ensure we are expanding our addressable population and providing inclusive polygenic risk scores for multi-ethnic populations.

Professor Colditz is a world-renowned figure in breast cancer epidemiology and risk modeling, and notable genotype datasets on the African American population are held by the Institute for Public Health. Given the USs multi-ethnic landscape, clinical applications will be affected by how the risk model performs in these populations.

Richard Allman, GTGs Chief Scientific Officer, will be heading the initiative and said, Our aim is to develop the best practical risk assessment tool for breast cancer. We hypothesise that a risk prediction model that is easy to answer while containing important risk-predicting information such as a polygenic risk score, a mammographic density risk score, and an absolute-risk, based on family history and selected clinical risk factors will provide better risk discrimination than any of the currently available individual risk models that do not incorporate all of these risk factors.

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Collaboration Aims to Improve GeneType Breast Cancer Test's Utility in African Americans - Clinical OMICs News

MCLEAN, Va., Oct. 1, 2021 /PRNewswire-PRWeb/ --The Multiple System Atrophy ("MSA") Coalition announces a ground-breaking million-dollar multi-year collaborative project focused on exploring the genetics of up to 1,200 people with either a diagnosis of probable MSA, in the case of living patients, or postmortem pathological confirmation of multiple system atrophy, aimed at locating commonalities in their genes that might contribute to the development of multiple system atrophy. The aim of this collaborative study is to sequence and organize the genomes of existing genetic samples as well as to organize previously sequenced whole-genome data into a single database that is accessible to researchers worldwide. While many researchers have looked at the genetics of MSA, this will be the first time such a large number of genomes from ethnically diverse populations have been sequenced and organized in such a way as to facilitate thorough analysis and collaborative enterprise.

"MSA is not typically passed from parent to child, except in extremely rare cases. However, there are still important clues about the underlying cause of MSA that can be found by examining the genetic code of a large population of MSA patients and looking for commonalities. Because MSA is a such a rare disease, there is a need for multiple researchers to work together and pool their data. Until now there has not been a concerted effort among genetic labs to combine these rare genetic samples from MSA patients with diverse backgrounds into a large, shared database," said Pam Bower, chair of the MSA Coalition's research committee. "The MSA Coalition is proud to be the driver of this ground-breaking study."

University of Florida will perform genetic sequencing under the direction of Matt Farrer, PhD, while storage, analysis and visualization of data will occur at Harvard Medical School in the Clinical Genome Analysis Platform ("CGAP") under the direction of Dana Vuzman, PhD. Additional genomic information will be provided by University College of London, Queen Square Institute of Neurology under the direction of Henry Houlden, MBBS, MRCP, PhD; by Translational Genomics Research Institute (TGen) under the direction of Matt Huentelman, PhD (Funded in part by the Rex Griswold Foundation, a grant from the NIH NINDS (R21-NS093222, PI: Huentelman), and through institutional support of TGen.); and by Seoul National University, under the direction of Beomseok Jeon, MD, PhD and Han-Joon Kim, MD, PhD. The Core G team also plans to coordinate their work with that being done at NIH under the direction of Sonja Scholz, MD, PhD. The group, collectively known as "Core G" (Genetics), will work closely with Vik Khurana, MD, PhD, board member and Scientific Liaison of the Board of Directors of the MSA Coalition and Chief of the Movement Disorders Division at Brigham and Women's Hospital and Harvard Medical School. Dr. Khurana will endeavor to integrate Core G team-member efforts more broadly into the MSA Collaborative Cores Initiative sponsored by the Coalition that will seed fund additional projects over time.

"I am thrilled that after years of planning and deliberation that Core G is funded and ready to go," said Khurana. "This group of terrific researchers, together with their expertise, bring precious patient samples from three continents to establish a foundation upon which other collaborations and initiatives will be built. We are under no illusion that the genetics of MSA will prove challenging, no less than a moonshot. At the same time, genetic insights promise to unlock powerful hypothesis-driven science that can find cures. And so, this moonshot is worth the effort and has been structured to be collaborative, open and sustainable in the long-term."

"We are incredibly proud of assembling this group of world-renowned researchers to collaborate on this project. It has taken almost three years to organize this project and obtain consents from all the institutions involved. Great care has been taken by all contributing institutions to safeguard the privacy of the patients and anonymize the genetic materials, so that patient privacy is protected," said Cynthia Roemer, MSA Coalition board chair. "We are also grateful to our many donors, who have made this project possible, and to the patients we have lost to MSA who generously left bequests to the MSA Coalition to further critical research like this. We quite literally could not do it without them!"

Dana Vuzman, PhD is an Instructor of Medicine at Harvard Medical School and the Director of Genomic Platform Development at DBMI. Dr. Vuzman oversees the implementation of the Clinical Genome Analysis Platform (CGAP) and the Single Cell RNA Platform in the Department. Prior to joining DBMI, she served as Chief Informatics Officer at One Brave Idea, Sr. Director of Biomedical Informatics at KEW, Inc., and Co-Director at Brigham Genomic Medicine. Dr. Vuzman earned her PhD in Computational Biology from the Weizmann Institute of Science in Israel and completed her postdoctoral training in Computational Genetics at Brigham and Women's Hospital and Harvard Medical School.

Matt Farrer, PhD is critically acclaimed for his work in the genetics and neuroscience of Parkinson's disease. His inspiration to apply genetic analysis to complex neurologic disorders came from early work as a care assistant of patients and families with neurologic and psychiatric disorders. Dr. Farrer earned his first degree in Biochemistry with a Doctoral degree in Molecular and Statistical Genetics from St. Mary's Hospital Medical School, UK. He completed a fellowship in Medical Genetics at the Kennedy-Galton Centre, UK and in Neurogenetics at Mayo Clinic. Dr. Farrer became an Assistant Professor of Molecular Neuroscience in 2000 where he opened his first laboratory to predict and prevent Parkinson's disease. Dr. Farrer became a tenured professor in 2006, a Mayo Consultant, and subsequently, a Distinguished Mayo Investigator. In 2010, Dr. Farrer was awarded a Canada Excellence Research Chair to build the Centre for Applied Neurogenetics and Neuroscience at the University of British Columbia, Vancouver, Canada where he became a Professor of Medical Genetics. The Province of British Columbia subsequently awarded him the Don Rix Chair in Precision Medicine, and his team had many notable accomplishments including several new genes and mouse models for Parkinson's disease. The team also implemented high-throughput sequencing in pediatric seizure disorders and neonatology in clinical service. The former was funded through the Medical Services Plan of British Columbia and was a first for Canada.

In 2019, Dr. Farrer accepted an endowed chair at the Norman Fixel Institute for Neurological Diseases (thanks to a generous endowment from the Lauren and Lee Fixel Family Foundation). Dr. Matt Farrer also directs the UF Clinical Genomics Program. As such he currently has appointments and affiliations in the UF College of Medicine's Neurology and Pathology Departments, Clinical and Translational Science Institute, the Evelyn F. and William L. McKnight Brain Institute, the Center for Translational Research in Neurodegenerative Disease, and the Center for Neurogenetic in addition to the Norman Fixel Institute for Neurological Diseases.

Henry Houlden, MBBS, MRCP, PhD: Dr. Houlden is a professor of neurology and neurogenetics in the Department of Neuromuscular Disease, University College, London, Queen Square Institute of Neurology, and undertakes research laboratory works on neurogenetics and movement disorders with a particular interest in rare diseases that are adult or childhood-onset, such as multiple system atrophy (MSA), spinocerebellar ataxia and other movement disorders, inherited neuromuscular conditions, and difficult to diagnose disorders, particularly in diverse and underrepresented populations. He assists with the integration of new gene discovery with exome and genome sequencing identifying disease genes such as CANVAS, NARS1, NKX-6.2, SCA11, SCA15, GRIA2, and GAD1, with functional experimental validation in human tissue and other model systems. Dr. Houlden has clinical expertise in inherited neurological disorders and movement disorders such as multiple system atrophy, ataxia, leukodystrophy, epilepsy and paroxysmal conditions, spastic paraplegia and neuromuscular conditions.

Matt Huentelman, PhD: Dr. Huentelman's research interests center around the investigation of the "-omics" (genomics, transcriptomics, and proteomics) of neurological traits and disease. His laboratory's overarching goal is to leverage findings in these disciplines to better understand, diagnose, and treat human diseases of the nervous system.

Dr. Huentelman joined TGen in July of 2004 after completing his doctoral work at the University of Florida's Department of Physiology and Functional Genomics at the McKnight Brain Institute where he investigated the application of gene therapy in the study and prevention of hypertension. His undergraduate degree is in Biochemistry from Ohio University's Department of Chemistry and Biochemistry at Clippinger Laboratories. Dr. Huentelman's career includes visiting researcher stints in Moscow, Russia at the MV Lomonosov Moscow State University "Biology Faculty" and in the United Kingdom within the University of Bristol's Department of Physiology.

Beomseok Jeon, MD, PhD: Professor Jeon is the medical director of the Movement Disorder Center, Seoul National University Hospital and is interested in genetics of Parkinsonism and medical and surgical treatment of advanced Parkinson's Disease.

Dr. Jeon earned his undergraduate, MD and PhD degrees from Seoul National University. His clinical interests include Parkinson's disease and other movement disorders including tremor, ataxia, dystonia, and chorea. His research focuses on the role of genetics in movement disorders, especially in the Korean population. He has established a DNA bank of thousands of Korean patients with movement disorders and normal controls. He is also involved in treatment of advanced Parkinson disease, and works with neurosurgical colleagues for various surgical treatment.

Han-Joon Kim, MD, PhD: Dr. Kim is a Professor in the Department of Neurology and the Movement Disorder Center at Seoul National University Hospital, Seoul, Korea. After graduation from the Medical College of Seoul National University in 1997, Dr. Kim took an internship and residency in neurology at Seoul National University Hospital (SNUH) where he became a Movement Disorder Specialist.

Clinically, Dr. Kim has experience with patients with various movement disorders including Parkinson's Disease (PD), Multiple System Atrophy (MSA), other atypical Parkinsonisms, and ataxias. Notably, Dr. Kim has set up a large registry of Korean MSA patients, which will serve as a basis for both observational and interventional studies in this rare disease.

Sonja W. Scholz, MD, PhD: Dr. Scholz is a Neurologist and Neurogeneticist specialized in movement and cognitive disorders. She received her medical degree from the Medical University Innsbruck, Austria. Following graduation, she was a post-doctoral fellow at the Laboratory of Neurogenetics at the NIH's National Institute on Aging (NIA) under the supervision of Drs. Andrew Singleton and John Hardy. She obtained a Ph.D. in Neurogenomics from the University College London, UK in 2010. She then moved to Baltimore to complete her neurology residency training at Johns Hopkins. In 2015, Dr. Scholz received the McFarland Transition to Independence Award for Neurologist-Scientists. She is a Lasker Clinical Research Tenure Track Investigator within the Neurogenetics Branch at the NIH's National Institute of Neurological Disorders and Stroke (NINDS). Her laboratory focuses on identifying genetic causes of neurodegenerative diseases, such as dementia with Lewy bodies, multiple system atrophy, and frontotemporal dementia.

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The Multiple System Atrophy Coalition Announces a Groundbreaking Project to Explore the Genetics of MSA - Johnson City Press (subscription)

NEW YORK, Sept. 29, 2021 /PRNewswire/ --The DeGregorio Family Foundationhas awarded$250,000 to Bryson Katona, MD, PhD, Assistant Professor of Medicine and Director at the Gastrointestinal Cancer Genetics Program at University of Pennsylvania Perelman School of Medicine. Dr. Katona is a physician-scientist who seeks to better define the gastric cancer risks associated with the CTNNA1 gene in order to aid both patients and medical professionals in their abilities to manage the cancer risks associated with the gene.

Hereditary diffuse gastric cancer syndrome (HDGC), the most common cause of familial diffuse gastric cancer, leads to substantially increased gastric cancer risk that often necessitates the prophylactic removal of the stomach for cancer prevention.The CDH1 gene was the first gene found to be associated with HDGC and remains the most common and best characterized gene associated with this condition.More recently, the CTNNA1 gene has also been shown to be associated with HDGC; however, given limitations in the amount of available data, the true gastric cancer risk for carriers of an abnormal CTNNA1 gene remain uncertain.

With support from the DeGregorio Family Foundation Grant Award, Dr. Katona's lab plans to conduct an international study to allow collection of cancer information from families who carry a CTNNA1 gene variant, which will allow him and his team to calculate the cancer risks associated with this gene. Secondly, they will utilize gastric organoids, which are novel three-dimensional models of gastric tissue that are derived directly from biopsies of the stomach, to study how different changes in the CTNNA1 gene may contribute to gastric cancer growth.

In 2020, gastric and esophageal cancers combined to kill over 1.3 million people worldwide making it the second-leading cause of cancer-related death. Patients continue to face poor prognoses following gastric and esophageal cancer diagnoses due to their chemo-resistant behavior and ability to metastasize.

The DeGregorio Family Foundation, founded in 2006 after a 10th member of the DeGregorio family died of stomach cancer, has raised more than $5 million to fund innovative research focused on curing gastric and esophageal cancers. Lynn DeGregorio, President and Founder, stated, "We are so thankful for the support we have received and honored to award grants to projects that have the capacity to change the paradigm for those impacted by these diseases."

Commenting on his award, Dr. Katona said, "I am absolutely thrilled to be selected as a recipient of the DeGregorio Family Foundation Grant Award.This award will be instrumental in advancing our understanding of the hereditary diffuse gastric cancer syndrome risk gene CTNNA1, which will help inform future clinical care as well as cancer risk reduction strategies for CTNNA1 carriers."

Media Contact: Sarah Fletcher 917-855-7994 [emailprotected]

SOURCE DeGregorio Family Foundation

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Grant Awarded to Better Define Gastric Cancer Risks of the Hereditary Diffuse Gastric Cancer Gene CTNNA1 - PRNewswire

Parasites could become part of the armour of military personnel and first responders to help them counter chemical and biological weapon attacks in war zones.

Charles River Analytics announced Sep. 14 it was awarded a contract by the Defense Advanced Research Projects Agency (DARPA) to lead a team of research organizations seeking to develop a novel biosystem solution to protect warfighters from chemical and biological threats. The five-year, $16M contract will focus on neutralizing threats at vulnerable internal tissue barriers (including skin, airway, and ocular barriers) using a configurable biological countermeasure.

The effort is part of DARPAs Personalized Protective Biosystem (PPB) program, which is exploring the use of new transgenic commensal organismsspecifically hookworms and schistosomesto secrete therapeutics specifically targeting chemical and biological threats, including neurotoxins (such as organophosphates) and microbial pathogens.

These organisms already live naturally in humans in areas where they are endemic. They have sophisticated secretory systems that can be manipulated to provide immunotherapies to protect our women and men on the battlefield, said Dr. Bethany Bracken, Principal Scientist at Charles River Analytics and lead of the effort. Our goal is to insert a genetic sequence that provides the managed protection that the human body needs to counter these biological threats.

The effort includes a team of subcontractors including Baylor College of Medicine; George Washington University; James Cook University; Leiden University Medical Center; University of California, Irvine; and Washington University School of Medicine in St. Louis.

Professor Alex Loukas and Dr. Paul Giacomins teams from James Cook Universitys Australian Institute of Tropical Health and Medicine will receive nearly US $2.5 million over five years to conduct research as part of the effort.

Professor Loukas, a molecular parasitologist, said the project is intended to reduce the burden of personal protective equipment worn or carried by members of the military and medical first responders in conflict zones to protect them against bioterrorism agents.

What we will be doing at JCU builds on our work with parasitic helminth infections in human volunteers, said Professor Loukas.

Capitalising on recent advances in genetic modification using CRISPR-Cas9, the team will create parasitic helminths that secrete drugs that counteract bioterrorism agents, and thereby protect the parasite-infected subject against chemical and biological agents in a safe and well tolerated manner.

Professor Loukas said as military technology and technology in general advances, these kinds of threats will become more common.

It is clearly an advantage to have an internal biological solution to counter threats when they suddenly appear.

We are thinking of parasitic helminths as internal molecular foundries, producing and delivering drugs within and throughout the body continuously, or on demand, if we so choose, said Professor Loukas.

The George Washington University has been awarded a $3.6 million contract to genetically modify commensal organisms to produce antidotes for harmful biological and chemical agents.

We are genetically modifying the organisms responsible for the neglected tropical disease, schistosomiasis, to instead serve as a platform for delivering antibodies to frontline personnel who risk exposure to biological pathogens or harmful chemicals, Paul Brindley, PhD, professor of microbiology, immunology, and tropical medicine at the GW School of Medicine and Health Sciences and lead investigator on the project at GW, said. Our goal is to create an anti-threat solution that can be activated in 10 minutes or less and can be quickly adapted for new threats.

Brindley and his lab colleagues at GW have expertise inusing CRISPR/Cas9 to limit the impact of schistosomiasisand liver fluke infection. Because the agents that cause these diseases are adept at entering and circulating in the human body, they represent a potentially promising delivery vehicle for carrying antibody genes into the body as well. Brindley will use CRISPR/Cas9 to plug genetic information into the DNA of male organisms. As the organisms cycle through their life, the team aims to manipulate the experimentally gene-edited segment of genetic material, or transgene, to perform programmed tasks, such as turning on and off and releasing an anti-pathogen antibody into the body. Brindley and his research team will work in concert with military labs to test against real threats.

The first phase of the contract is 24 months. If successful, additional funding will be received to progress to phase two (also 24 months) and then phase three (12 months).

We have fascinating work ahead, which could bring tremendous protective measures first to our warfighters and eventually to the medical community overall, said Rich Wronski, Program Manager for the PPB effort and Vice President and Principal Scientist at Charles River Analytics. Our team spans four countries and 14 time zones to include the worlds foremost experts on hookworms and schistosomes.

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Protective Biosystems: Parasites to Fight Chemical and Biological Weapons - Global Biodefense

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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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.

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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.

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