Category Archives: Gene Medicine

How often a person takes daytime naps, if at all, is partly regulated by their genes, according to new research led by investigators at Harvard-affiliated Massachusetts General Hospital (MGH) and published inNature Communications.

In this study, the largest of its kind ever conducted, the MGH team collaborated with colleagues at the University of Murcia in Spain and several other institutions to identify dozens of gene regions that govern the tendency to take naps during the day. They also uncovered preliminary evidence linking napping habits to cardiometabolic health.

Napping is somewhat controversial, says Hassan Saeed Dashti of the MGH Center for Genomic Medicine, co-lead author of the report with Iyas Daghlas, a medical student at Harvard Medical School (HMS). Dashti notes that some countries where daytime naps have long been part of the culture (such as Spain) now discourage the habit. Meanwhile, some companies in the United States now promote napping as a way to boost productivity. It was important to try to disentangle the biological pathways that contribute to why we nap, says Dashti.

Previously, co-senior author Richa Saxena, principal investigator at the Saxena Lab at MGH, and her colleagues used massive databases of genetic and lifestyle information to study other aspects of sleep. Notably, the team has identified genes associated with sleep duration, insomnia, and the tendency to be an early riser or night owl. To gain a better understanding of the genetics of napping, Saxenas team and co-senior author Marta Garaulet of the department of physiology at the University of Murcia, performed a genome-wide association study (GWAS), which involves rapid scanning of complete sets of DNA, or genomes, of a large number of people. The goal of a GWAS is to identify genetic variations that are associated with a specific disease or, in this case, habit.

For this study, the MGH researchers and their colleagues used data from the UK Biobank, which includes genetic information from 452,633 people. All participants were asked whether they nap during the day never/rarely, sometimes or usually. The GWAS identified 123 regions in the human genome that are associated with daytime napping. A subset of participants wore activity monitors called accelerometers, which provide data about daytime sedentary behavior, which can be an indicator of napping. This objective data indicated that the self-reports about napping were accurate. That gave an extra layer of confidence that what we found is real and not an artifact, says Dashti.

Several other features of the study bolster its results. For example, the researchers independently replicated their findings in an analysis of the genomes of 541,333 people collected by 23andMe, the consumer genetic-testing company. Also, a significant number of the genes near or at regions identified by the GWAS are already known to play a role in sleep. One example isKSR2, a gene that the MGH team and collaborators had previously found plays a role in sleep regulation.

Digging deeper into the data, the team identified at least three potential mechanisms that promote napping:

This tells us that daytime napping is biologically driven and not just an environmental or behavioral choice, says Dashti.

Some of these subtypes were linked to cardiometabolic health concerns, such as large waist circumference and elevated blood pressure, though more research on those associations is needed.

Future work may help to develop personalized recommendations for siesta, says Garaulet.

Furthermore, several gene variants linked to napping were already associated with signaling by a neuropeptide called orexin, which plays a role in wakefulness. This pathway is known to be involved in rare sleep disorders like narcolepsy, but our findings show that smaller perturbations in the pathway can explain why some people nap more than others, says Daghlas.

Saxena is the Phyllis and Jerome Lyle Rappaport MGH Research Scholar at the Center for Genomic Medicine and an associate professor of anesthesia at HMS.

The work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, MGH Research Scholar Fund, Spanish Government of Investigation, Development and Innovation, the Autonomous Community of the Region of Murcia through the Seneca Foundation, Academy of Finland, Instrumentarium Science Foundation, Yrj Jahnsson Foundation, and Medical Research Council.

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The science behind those afternoon naps Harvard Gazette - Harvard Gazette

PROVIDENCE, R.I.[Brown University] New research provides insights into the treatment of Christianson syndrome (CS), an X-linked genetic disease characterized by reduced brain growth after birth, intellectual disability, epilepsy and difficulties with balance and speech.

One of the major challenges in developing treatments for human brain disorders, like CS, is developing an experimental system for testing potential therapeutics on human neurons, said study senior author Dr. Eric Morrow, an associate professor of molecular biology, neuroscience and psychiatry at Brown University. In recent years, advanced stem cell therapies that use tissues from patients have provided powerful new approaches for engineering human neurons from the patients themselves, who may undergo the treatment in the future.

For the study, published in Science Translational Medicine on Feb. 10, 2021, Morrow and his colleagues obtained blood samples from five CS patients and the patients unaffected brothers. They then reprogrammed these blood cells into stem cells, and these stem cells were converted into neurons in a petri dish. As a result, they obtained neurons that were representative of those from CS patients, and they used these neurons to test treatments.

Morrow who directs the Center for Translational Neuroscience at the Carney Institute for Brain Science and the Brown Institute for Translational Science said the team also used a new gene-editing approach that employs CRISPR-Cas9 technologies to correct patient mutations back to a healthy gene sequence.

CS is caused by a mutation in a gene encoding for NHE6, a protein that helps regulate acid levels within cell structures called endosomes. Past research suggests that the loss of NHE6 causes endosomes to become overly acidic, which disrupts the abilities of developing neurons to branch out and form connections in the growing brain.

Loss of this important protein can arise from a variety of gene mutations in patients. The majority of CS mutations are called nonsense mutations, which prevent NHE6 from being produced at all; four of the five CS patients involved in this study exhibited this class of mutation. However, some CS patients exhibit missense mutations. Individuals with missense mutations still have some NHE6, but it is produced in smaller amounts, and the protein fails to function as it should.

The research team tested two main forms of treatment on the stem-cell-derived neurons: first, gene transfer, which involves adding a healthy NHE6 gene into the cell; and second, administration of trophic factors, which are substances that promote neuron growth and encourage neurons to develop connections with other neurons. The researchers found that the neurons response to treatment depended on the class of mutation present.

The gene transfer studies, which may represent the first steps toward developing gene therapy, were successful in neurons with nonsense mutations. After the researchers inserted a functional NHE6 gene into nonsense-mutation CS neurons, the neurons branched out properly. In neurons with missense mutations, however, gene transfer failed completely. Further tests suggested that the abnormal NHE6 produced as a result of missense mutations may interfere with normal NHE6, thereby rendering gene transfer therapy ineffective in patient cells with these mutations.

In contrast, administration of trophic factors, such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), successfully promoted proper branching in all the CS neurons studied, regardless of mutation type.

While these initial results are encouraging, Morrow hopes that future studies will examine these treatments in animal models.

Our results provide an initial proof-of-concept for these treatment strategies, indicating that they should be studied further, he said. However, we may ultimately need to pay close attention to the class of mutation that a patient has when we choose a specific treatment.

In addition to Morrow, the research team included scientists from Brown University, the University of South Carolina and the Icahn School of Medicine at Mount Sinai. The study was supported by multiple grants from the National Institutes of Health as well as a number of awards from foundations and academic institutions.

This news story was authored by contributing science writerKerry Benson.

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Neurons from patient blood cells enable researchers to test treatments for genetic brain disease - Brown University

A scanning electron micrograph of an oral squamous cancer cell (white) being attacked by two cytotoxic T cells (red), part of a natural immune response. Image by NIH

For all their importance as a breakthrough treatment, the cancer immunotherapies known as checkpoint inhibitors still only benefit a small minority of patients, perhaps 15 percent across different types of cancer. Moreover, doctors cannot accurately predict which of their patients will respond.

A new study finds that inherited genetic variation plays a role in who is likely to benefit from checkpoint inhibitors, which release the immune systems brakes so it can attack cancer. The study also points to potential new targets that could help even more patients unleash their immune systems natural power to fight off malignant cells.

People who respond best to immunotherapy tend to have inflamed tumors that have been infiltrated by immune cells that are capable of killing both viruses and cancer. This inflammation is also driven by the immune signaling molecule interferon.

There are some factors that are already associated with how well the immune system responds to tumors, said Elad Ziv, MD, professor of medicine at UCSF and co-senior author of the paper, published Feb. 9, 2021, by an international team in Immunity. But whats been less studied is how well your genetic background predicts your immune systems response to the cancer. Thats what is being filled in by this work: How much is the immune response to cancer affected by your inherited genetic variation?

The study suggests that, for a range of important immune functions, as much as 20 percent of the variation in how different peoples immune systems are able to attack cancer is due to the kind of genes they were born with, which are known as germline genetic variations.

That is a significant effect, similar to the size of the genetic contribution to traits like high blood sugar levels or obesity.

Rather than testing selected genes, we analyzed all the genetic variants we could detect across the entire genome. Among all of them, the ones with the greatest effect on the immune systems response to the tumor were related to interferon signaling. Some of these variants are known to affect our response to viruses and our risk of autoimmune disorders, said Davide Bedognetti, MD, PhD, director of the Cancer Program at the Sidra Medicine Research Branch in Doha, Qatar, and co-senior author of the paper. As observed with other diseases, we demonstrated that specific genes can also predispose someone to have a more effective anti-cancer immunity.

The team identified variants in 22 regions in the genome, or in individual genes, with significant effects including one gene, IFIH1, that is already well known for the role its variants play in autoimmune diseases as varied as type 1 diabetes, psoriasis, vitiligo, systemic lupus erythematosus, ulcerative colitis and Crohns disease.

The IFIH1 variants act on cancer immunity in different ways. For instance, people with the variant that confers risk of type 1 diabetes had a more inflamed tumor, which suggests they would respond better to cancer immunotherapy. But the researchers saw the opposite effect for patients with the variant associated with Crohns, indicating they might not benefit.

Another gene, STING1, was already thought to play a role in how patients respond to immunotherapy, and drug companies are looking for ways to boost its effects. But the team discovered that some people carry a variant that makes them less likely to respond, which may require further stratification of patients to know who could benefit most from those efforts.

The study required a huge amount of data that could only be found in a dataset as large as The Cancer Genome Atlas (TCGA), and from which they analyzed the genes and immune responses of 9,000 patients with 30 different kinds of cancer.

All told, the scientific team, which includes members from the United States, Qatar, Canada, and Europe, examined nearly 11 million gene variants to see how they matched with 139 immune parameters measured in patient tumor samples.

But the 22 regions or genes identified in the new study are just the tip of the iceberg, the researchers said, and they suspect many more germline genes likely play a role in how the immune system responds to cancer.

The next step, Ziv said, is to use the data to formulate polygenic approaches taking a large number of genes into account to predict which cancer patients will benefit from current therapies, and developing new drugs for those who will not.

Its further off, he said, but its a big part of what we hope will come out of this work.

The co-first authors are Rosalyn Sayaman, PhD, at UCSF and City of Hope and Mohamad Saad, PhD, of Qatar Computing Research Institute at Hamad Bin Khalifa University in Doha, Qatar. See the paper online for additional author, funding and disclosure information.

The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.UCSF Health, which serves as UCSFs primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area.

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Response to Cancer Immunotherapy May Be Affected by Genes We Carry from Birth - UCSF News Services

ALISO VIEJO, Calif., Feb. 10, 2021 /PRNewswire-PRWeb/ -- RARE-X today announced three new board members who will help support the nonprofit's work in structured patient data collection, responsible data sharing, and the promise of its Federated Data Sharing Platform for data sharing and analysis. The new board members are Cynthia Grossman, PhD, director at Biogen; Jason Colquitt, CEO of Across Healthcare; and Simon Frost, CEO of Tiber Capital Group.

"The additions of Cynthia Grossman, PhD, Jason Colquitt, and Simon Frost to the board are very strategic. All bring a depth of knowledge in patient advocacy, health tech, scaling-up organizations, and operational excellence," said Nicole Boice, RARE-X Co-Founder/Executive Director. "We are honored to have them join an already extraordinary board and thrilled to channel their expertise, talent, and energy into helping RARE-X build towards the future."

Cynthia Grossman, PhD, is a director at Biogen, leading the MS PATHS program, a collaborative research network aimed at generating evidence to improve outcomes for patients living with Multiple Sclerosis. Prior to joining Biogen, Cynthia was director at FasterCures, a center of the Milken Institute. Before joining FasterCures, she was chief of the HIV Care Engagement and Secondary Prevention Program in the Division of AIDS Research (DAR) at the National Institute of Mental Health (NIMH). Cynthia has spent her career working to improve health by expanding opportunities for patients' perspectives to shape the processes by which new therapies are discovered, developed, and delivered. Cynthia graduated Phi Beta Kappa from Earlham College with a B.A. in psychology and biology and earned her Ph.D. in clinical psychology from the University of Vermont. She has been the recipient of a National Science Foundation Incentives for Excellence Scholarship, an NIH Ruth L. Kirschstein National Research Services Award, and a Postdoctoral Fellowship in Pediatric Psychology at the Warren Alpert Medical School of Brown University.

Jason Colquitt is CEO of Across Healthcare, a company he founded in 2012, leveraging his 20+ years in the healthcare technology field. His work has caused positive disruption within the healthcare industry as he has partnered with many organizations ranging from small start-ups to some of the world's largest health companies including Greenway Health, Walgreens Boots Alliance, Quintiles, IQVIA, Cystic Fibrosis Foundation, Muscular Dystrophy Association, American College of Surgeons, and American Heart Association. Jason has worked directly with patients, caregivers, physicians, regulators, and researchers. Jason was diagnosed with Carnitine Palmitoyltransferase II Deficiency (CPT II), a rare mitochondrial disease. He has used his experiences and technical background to help the rare disease community. Jason holds a Bachelor's degree in Applied Mathematics from Auburn University.

Simon Frost is the CEO of Tiber Capital Group. Before joining Tiber Capital Group, he was the chief investment officer of Greencourt Capital, a public company with approximately $1 billion in real estate assets. Before joining Greencourt Capital, Simon was president and COO of Key Properties. He was also the co-founder of The American Home, one of the largest single-family rental aggregators in the United States. Simon holds Bachelor's and Master's degrees in economics from Cambridge University in England, and a Bachelor's degree in finance from the University of South Africa. Simon serves as director of both Cure AHC and Hope For Annabel, charities dedicated to finding therapies for Alternating Hemiplegia of Childhood.

The current RARE-X Board of Directors includes: Betsy Bogard, head of program and alliance management within the 4:59 Initiative at 5AM Ventures; Nicole Boice, co-founder and executive director of RARE-X; Jason Colquitt, CEO of Across Healthcare; Wendy Erler, vice president of Patient Experience, STAR and Advocacy at Alexion Pharmaceuticals; Simon Frost, CEO of Tiber Capital Group; Peter Goodhand, CEO of Global Alliance for Genomics and Health; Cynthia Grossman, PhD, director at Biogen; Walt Kowtoniuk, PhD, COO of MOMA Therapeutics and venture partner at Third Rock Ventures; Craig Martin, president of Rithm Health and interim CEO at Global Genes; Katherine Maynard, principal at PWR; Angeli Moeller, PhD, head of Pharma Informatics International at Roche; David Pearce, PhD, president of Innovation and Research for Sanford Health; Anthony Philippakis, MD, PhD, chief data officer at Broad Institute; John Reynders, PhD, chief data scientist at Reynders Consulting; Morrie Ruffin, co-founder and board member of ARM Foundation for Cell and Gene Medicine and managing partner, Adjuvant Partners; Alvin Shih, MD, president and CEO at Catamaran Bio.

ABOUT RARE-X

RARE-X is a 501(c)(3) patient advocacy organization focused on supporting the acceleration and development of life-altering treatments and future cures for patients impacted by rare disease. Enabled by best-in-class technology, patients, researchers, and other technology vendors, RARE-X will gather structured, fit-for-purpose data to share broadly, benefitting from 21st-century governance, consent, and federated data sharing technology. RARE-X is building the largest collaborative patient-driven, open-data access project for rare diseases globally. For more information, visit http://www.rare-x.org.

Media Contact:

Tom Hume, Marketing Communications RARE-X

tomh@rare-x.org

Media Contact

Tom Hume, RARE-X, 7602144863, tomh@rare-x.org

SOURCE RARE-X

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RARE-X Announces the Expansion of its Board of Directors to Support the Organization's Growth and Launch Efforts - WFMZ Allentown

Key Points:Question: Can a genomic biomarker estimate the risk of prostate cancer clinical endpoints in men who received salvage radiation for rising prostate-specific antigen levels after surgery?

Findings: In this ancillary study of 352 men randomized to placebo or hormone therapy in the NRG/RTOG 9601 clinical trial of salvage radiation, the Decipher genomic classifier was independently associated with the risk of metastasis, prostate cancerspecific mortality, and overall survival.

Meaning: These findings suggest that the Decipher genomic classifier is a promising biomarker to risk stratify men to better enable hormone therapy treatment decisions for biochemical recurrence of their prostate cancer after surgery.

Abstract:Importance: Decipher (Decipher Biosciences Inc) is a genomic classifier (GC) developed to estimate the risk of distant metastasis (DM) after radical prostatectomy (RP) in patients with prostate cancer.

Objective: To validate the GC in the context of a randomized phase 3 trial.

Design, Setting, and Participants: This ancillary study used RP specimens from the phase 3 placebo-controlled NRG/RTOG 9601 randomized clinical trial conducted from March 1998 to March 2003. The specimens were centrally reviewed, and RNA was extracted from the highest-grade tumor available in 2019 with a median follow-up of 13 years. Clinical-grade whole transcriptomes from samples passing quality control were assigned GC scores (scale, 0-1). A National Clinical Trials Networkapproved prespecified statistical plan included the primary objective of validating the independent prognostic ability of GC for DM, with secondary endpoints of prostate cancer-specific mortality (PCSM) and overall survival (OS). Data were analyzed from September 2019 to December 2019.

Intervention: Salvage radiotherapy (sRT) with or without 2 years of bicalutamide.

Main Outcomes and Measures: The preplanned primary endpoint of this study was the independent association of the GC with the development of DM.

Results: In this ancillary study of specimens from a phase 3 randomized clinical trial, GC scores were generated from 486 of 760 randomized patients with a median follow-up of 13 years; samples from a total of 352 men (median [interquartile range] age, 64.5 (60-70) years; 314 White [89.2%] participants) passed microarray quality control and comprised the final cohort for analysis. On multivariable analysis, the GC (continuous variable, per 0.1 unit) was independently associated with DM (hazard ratio [HR], 1.17; 95% CI, 1.05-1.32; P = .006), PCSM (HR, 1.39; 95% CI, 1.20-1.63; P < .001), and OS (HR, 1.17; 95% CI, 1.06-1.29; P = .002) after adjusting for age, race/ethnicity, Gleason score, T stage, margin status, entry prostate-specific antigen, and treatment arm. Although the originally planned analysis was not powered to detect a treatment effect interaction by GC score, the estimated absolute effect of bicalutamide on 12-year OS was less when comparing patients with lower vs higher GC scores (2.4% vs 8.9%), which was further demonstrated in men receiving early sRT at a prostate-specific antigen level lower than 0.7 ng/mL (7.8% vs 4.6%).

Conclusions and Relevance: This ancillary validation study of the Decipher GC in a randomized trial cohort demonstrated association of the GC with DM, PCSM, and OS independent of standard clinicopathologic variables. These results suggest that not all men with biochemically recurrent prostate cancer after surgery benefit equally from the addition of hormone therapy to sRT.

Trial Registration ClinicalTrials.gov identifier: NCT00002874

Authors: Felix Y. Feng, MD; Huei-Chung Huang, MA; Daniel E. Spratt, MD; Shuang (George) Zhao, MD; Howard M. Sandler, MD; Jeffry P. Simko, MD, PhD; Elai Davicioni, PhD; Paul L. Nguyen, MD; Alan Pollack, MD, PhD; Jason A. Efstathiou, MD, PhD; Adam P. Dicker, MD, PhD; Tamara Todorovic, MSc; Jennifer Margrave, BSc; Yang (Seagle) Liu, PhD; Bashar Dabbas, MD; Darby J. S. Thompson, PhD; Rajdeep Das, MD, PhD; James J. Dignam, PhD; Christopher Sweeney, MD; Gerhardt Attard, PhD; Jean-Paul Bahary, MD; Himanshu R. Lukka, MD; William A. Hall, MD; Thomas M. Pisansky, MD; Amit B. Shah, MD; Stephanie L. Pugh, PhD; William U. Shipley, MD; Phuoc T. Tran, MD, PhD

Department of Radiation Oncology, UCSF Medical Center, San Francisco, California (Feng, Das); Department of Medicine, UCSF Medical Center, San Francisco, California (Feng, Das); Department of Urology, UCSF Medical Center, San Francisco, California (Feng, Das); Decipher Biosciences, San Diego, California (Huang, Davicioni, Todorovic, Margrave, Liu, Dabbas); Department of Radiation Oncology, University of Michigan, Ann Arbor (Spratt, Zhao); Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California (Sandler); NRG Biorepository, Department of Pathology, UCSF Medical Center, San Francisco, California (Simko); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (Nguyen); Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (Pollack); Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (Efstathiou, Shipley); Department of Radiation Oncology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (Dicker); Emmes Canada, Vancouver, British Columbia, Canada (Thompson); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (Dignam, Pugh); Department of Public Health, University of Chicago, Chicago, Illinois (Dignam); Department of Medicine, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts (Sweeney); Department of Oncology, University College London, London, United Kingdom (Attard); Department of Radiation Oncology, Centre Hospitalier de lUniversit de Montral-Notre Dame, Montreal, Quebec, Canada (Bahary); Department of Radiation Oncology, Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, Ontario, Canada (Lukka); Department of Radiation Oncology, Froedtert and the Medical College of Wisconsin, Madison, Wisconsin (Hall); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (Pisansky); Department of Radiation Oncology, WellSpan Health-York Cancer Center accruals under Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (Shah); Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland (Tran); Department of Oncology, Johns Hopkins University, Baltimore, Maryland (Tran); Department of Urology, Johns Hopkins University, Baltimore, Maryland (Tran).

Source: Feng F, Huang HC, Spratt D et al."Validation of a 22-Gene Genomic Classifier in Patients With Recurrent Prostate Cancer An Ancillary Study of the NRG/RTOG 9601 Randomized Clinical Trial." JAMA Oncology. 2021.2020.7671.

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Genomic Test Helps Guide Precision Medicine to Estimate Risk of Prostate Cancer Metastasis, Death

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Validation of a 22-Gene Genomic Classifier in Patients With Recurrent Prostate Cancer An Ancillary Study of... - UroToday

BOSTON--(BUSINESS WIRE)--Ensoma, a company expanding the curative power of genomic medicine by pioneering a next-generation in vivo approach, today launched with a $70 million Series A financing led by co-founder and seed investor 5AM Ventures, with participation from F-Prime Capital, Takeda Ventures, Viking Global Investors, Cormorant Asset Management, RIT Capital Partners, Symbiosis II, LLC, and Alexandria Venture Investments. In addition to an equity investment of $10 million in the Series A financing, Takeda Pharmaceutical Company Limited (Takeda) and Ensoma have entered into a strategic collaboration with the potential for upfront and preclinical research payments totaling $100 million as part of a strategic collaboration worth up to $1.25 billion, announced in a separate press release this morning.

The foundation of the companys platform its Engenious vectors is based on over two decades of academic and clinical research generated by scientific co-founders and renowned experts, Hans-Peter Kiem, M.D., Ph.D., of Fred Hutchinson Cancer Research Center, and Andr Lieber, M.D., Ph.D., of University of Washington School of Medicine. The company will be led by biotechnology industry veterans with demonstrated track records in innovative therapeutic modalities, including gene therapy and editing, across an array of disease areas, including rare disease, hematology and oncology.

Ensomas Engenious vectors are designed to deliver a diverse range of genome modification technologies including those that require a high level of packaging capacity directly to hematopoietic stem cells (HSCs) or the various cell types that arise from these cells, such as T cells, B cells and myeloid cells. The companys vectors are optimized to work without the need for stem cell collection or prior myeloablative conditioning (e.g., chemotherapy). As a result, Ensomas therapies will be designed to be delivered via single injection in diverse environments, including outpatient and areas where access to sophisticated healthcare systems may be limited.

With the launch of Ensoma, we aspire to bring innovative new treatments to patients in a way that is accessible for all, said Paula Soteropoulos, executive chairman of Ensoma. Because our in vivo therapies do not require prior conditioning or stem cell donors, we hope to deliver them as off-the-shelf treatments to address diseases both rare and common dramatically simplifying the logistics of scaling production and reducing patient and healthcare-system burden. Every person, no matter where they are in the world, should have access to the innovative technologies that are changing the way we treat disease.

Engenious Vectors

Ensomas Engenious vectors are specially engineered adenovirus vectors devoid of any viral genome and minimal pre-existing immunity, thus minimizing the chance of an immune response and freeing up ample storage space up to 35 kilobases (kb) of DNA packaging capacity to deliver a diverse range of genome modification technologies. Also known as therapeutic cargo, these technologies may include, separately and in combination, the following:

These approaches enable Engenious vectors to engineer various erythroid, lymphoid (e.g., T cells, B cells) and myeloid (e.g., macrophages, microglia) cell types, with great precision and vast therapeutic potential. Addressable indications range from rare monogenic diseases to broader diseases such as oncology, autoimmunity and infectious diseases via precision, off-the-shelf engineering of the immune system.

Given the highly specific nature of these technologies, Ensomas Engenious vectors enable preferential targeting of HSCs inside the body. Additionally, Ensomas founders have developed an in vivo selection system that can increase the population of genetically modified HSCs, if needed. This proprietary approach enables precise titration to lasting therapeutic levels without the need to re-dose patients, bypassing the immunogenic challenges associated with re-dosing for some other gene therapy modalities.

Ensomas Engenious platform has been extensively validated in numerous preclinical models with a range of genome editing technologies, demonstrating robust genetic modification of bone marrow HSCs and stable long-term expression of therapeutic proteins in small and large preclinical models.

There have been tremendous advancements in technologies to precisely target, genetically edit and modify human disease. However, many of these tools pose delivery challenges; some lack the ability to reach the right cells within the body, while others lack the ability to broadly reach significant numbers of patients due to complex procedures and supply chain challenges, said Kush M. Parmar, M.D., Ph.D., founding chief executive officer of Ensoma. Ensomas scientific approach allows us to do what hasnt been done beforeto make the curative power of genomic medicine and stem cell technology portable so they may be administered in low-resource and outpatient settings for the very first time.

Leadership & Scientific Founders

Ensoma was founded by and incubated within the 4:59 Initiative, the company creation engine of 5AM Ventures. The companys scientific co-founders include Dr. Hans-Peter Kiem, an oncologist and world-renowned pioneer in gene-editing technologies, including stem cell and gene therapies, from Fred Hutch, who also serves as vice president of the American Society of Gene & Cell Therapy and chief scientific and clinical advisor for Ensoma; and Dr. Andr Lieber, an accomplished academic researcher and professor of medicine, Division of Medical Genetics, UW School of Medicine, who has studied the biological and translational aspects of human adenoviruses for more than two decades. Ensoma is based on an exclusively licensed portfolio of technologies developed by the Fred Hutch lab of Dr. Kiem and the University of Washington lab of Dr. Lieber that enable in vivo genome engineering and gene therapy advances of HSCs for therapeutic use in blood diseases.

Following more than 20 years of academic and clinical research, Ensoma has assembled an exceptional team to boldly forge a new era of genomic medicine in vivo, said Bihua Chen, founder and portfolio manager at Cormorant Asset Management. The company is moving swiftly to accelerate and broaden the therapeutic potential of its approach, and I am confident they have the right team and the right technology to potentially bring life-changing, curative therapies within reach for people all over the world.

Additional details surrounding company leadership, including its board of directors, are as follows:

Ensoma has also named its scientific advisory board, which may be viewed here.

About 5AM Ventures

Founded in 2002, 5AM actively invests in next-generation biotech companies. With approximately $1.5 billion raised since inception, 5AM has invested in 89 companies. For more information, please visit http://www.5amventures.com.

About the 4:59 Initiative

The 4:59 Initiative is the internal company creation engine at 5AM Ventures that helps discover, incubate, and fund breakthrough science. The 4:59 team provides hands-on scientific, strategic, and operational support, working closely with academics and entrepreneurs to advance breakthrough science and establish proof-of-concept data to enable a clear path to transformative therapies for patients.

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Ensoma Launches to Pioneer Next-Generation In Vivo Approach to Deliver First Off-the-shelf Genomic Medicines - Business Wire

LONDON and LAUPHEIM, Germany, Feb. 11, 2021 (GLOBE NEWSWIRE) -- The Cell and Gene Therapy Catapult (CGT Catapult), an independent centre of excellence in innovation advancing the UKs cell and gene therapy industry, and Rentschler Biopharma SE, a leading global contract development and manufacturing organisation (CDMO) for biopharmaceuticals, have announced today that Rentschler Biopharma will establish their manufacturing capability in Advanced Therapy Medicinal Products (ATMPs), including Adeno-Associated Virus (AAV) Vectors for clinical trial supply, at the CGT Catapult site in Stevenage.

Under the terms of the agreement, Rentschler Biopharma will make a significant investment at the site over the next five years to set up their manufacturing capabilities, benefitting from the expertise and unique collaborative model provided by the CGT Catapult. The companys investment is expected to make a major contribution to meeting the demand from UK and international researchers for suitable manufacturing capability. This development will further strengthen the UK ecosystem through the addition of Rentschler Biopharmas more than 40 years of experience and solid reputation in the development and manufacturing of biologics for both clinical and commercial supply. The company will leverage the CGT Catapults expertise in ATMP manufacturing setup and technology development, as well as the cell and gene therapy cluster and ecosystem that has developed around Stevenage and across the UK.

Dr. Frank Mathias, CEO of Rentschler Biopharma, said:We are excited to take this next big step in our evolution and address the growing industry demand for ATMP manufacturing capacity and viral vector supply. With the largest industry cluster for cell and gene therapies outside the US, the UK is an ideal location for us to establish our Center of Excellence for cell and gene therapy. We look forward to working with the CGT Catapult as we invest in this growing field. They are well established in this important market, enabling us to immediately tap into the organisations network and utilisethe UKs strong expertise and supply chain in cell and gene therapy manufacturing.

Matthew Durdy, CEO of the Cell and Gene Therapy Catapult, commented:We are very pleased that Rentschler Biopharma, a global CDMO, has chosen to build their ATMP capacity in the UK, bringing in their expertise and investment. This will build new capacity to benefit the international ATMP supply chain and meet growing academic and commercial demand across the industry. As more companies from around the globe come to the UK, it demonstrates and enhances the attractiveness of its cell and gene therapy ecosystem as a place to develop new technologies and capabilities.

The investment in the UK cell and gene therapy industry announced today is expected to further accelerate the development of the vital infrastructure and skilled jobs needed to meet the rising demand for manufacturing capacity in the UK and globally, as well as streamline the supply chain for these advanced therapies. Currently, 27% of European ATMP companies are operating in the UK, and there are more than 90 advanced therapy developers. The last year has also seen a 50% increase in the number of ATMP clinical trials being run in the UK, accounting for 12% of global ATMP clinical trials, and these numbers are predicted to increase further.

The CGT Catapult manufacturing centre has been backed by over 75m of funding, including investment from the UK Governments Industrial Strategy Challenge Fund, the Department for Business, Energy and Industrial Strategy, Innovate UK and from the European Regional Development Fund. Since it was announced, there has been over 1.1bn of investment in the ATMP industry in its vicinity.

About Rentschler Biopharma SE

Rentschler Biopharma is a leading contract development and manufacturing organization (CDMO), focused exclusively on client projects. The company offers process development and manufacturing of biopharmaceuticals as well as related consulting activities, including project management and regulatory support. Rentschler Biopharma's high quality is proven by its long-standing experience and excellence as a solution partner for its clients. A high-level quality management system, a well-established operational excellence philosophy and advanced technologies ensure product quality and productivity at each development and manufacturing step. In order to offer best-in-class formulation development along the biopharmaceutical value chain, the company has entered into a strategic alliance with Leukocare AG. Rentschler Biopharma is a family-owned company with about 1,000 employees, headquartered in Laupheim, Germany, with a second site in Milford, MA, USA. In Stevenage, UK, Rentschler Biopharma launched a company dedicated to cell and gene therapies, Rentschler ATMP Ltd.

For further information, please visit http://www.rentschler-biopharma.com. Follow Rentschler Biopharma on LinkedIn and Facebook.

About the Cell and Gene Therapy Catapult

The Cell and Gene Therapy Catapult was established as an independent centre of excellence to advance the growth of the UK cell and gene therapy industry, by bridging the gap between scientific research and full-scale commercialisation. With more than 330 employees focusing on cell and gene therapy technologies, it works with partners in academia and industry to ensure these life-changing therapies can be developed for use in health services throughout the world. It offers leading-edge capability, technology and innovation to enable companies to take products into clinical trials and provide clinical, process development, manufacturing, regulatory, health economics and market access expertise. Its aim is to make the UK the most compelling and logical choice for UK and international partners to develop and commercialise these advanced therapies. The Cell and Gene Therapy Catapult works with Innovate UK.

For more information please visit ct.catapult.org.uk or visit http://www.gov.uk/innovate-uk.

About the European Regional Development Fund

This project has received 3.36m of funding from the England European Regional Development Fund as part of the European Structural and Investment Funds Growth Programme 2014-2020. The Ministry of Housing, Communities and Local Government (and in London the intermediate body Greater London Authority) is the Managing Authority for European Regional Development Fund. Established by the European Union, the European Regional Development Fund helps local areas stimulate their economic development by investing in projects which will support innovation, businesses, create jobs and local community regenerations. For more information visit https://www.gov.uk/european-growth-funding.

About the Industrial Strategy Challenge Fund

This project has received 12m of funding from the Industrial Strategy Challenge Fund, part of the governments modern Industrial Strategy. The Industrial Strategy Challenge Fund is a four-year, 1 billion investment in cutting-edge technology designed to create jobs and improve living standards, built on guidance from business and the academic community. Healthcare and Medicine is one of three core areas for investment under the programme.

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Rentschler Biopharma to build new cell and gene therapy capabilities in the UK - BioSpace

If theres one thing Ive learned over the years as a health and wellness writer, its that information is power. The flip side of that is the fact that not having key information available to you can be deeply disempowering. Like millions of other Americans, Im adopted, which means I havent been able to find out a lot about important health information that most people have readily available to them: family health history and genetic health information.

Family health history is essentially just that: knowing the health histories of members of your biological family. This kind of information can help doctors pinpoint whether you are at risk for certain health conditions that can run in families or be determined by genetics. Family history is a strong clue for chronic disease risks you may face, such as heart disease, stroke, cancer, and diabetes, says Latha Palaniappan, MD, the scientific director of Genomics and Pharmacogenomics in Primary Care at Stanford Medicine. The Centers for Disease Control and Prevention (CDC) CDC recommends documenting as much as you can about your familys health history in order to share with your doctor, and ask for additional testing if youre concerned about your risk for a specific disease.

While Ive always valued a healthy lifestyleI try to eat well, sleep enough, exercise, and manage stress as much as possibleIve wondered recently if my inclination towards healthy living has been driven in part by fear, specifically the fear of what I dont know about my health and genetics. Since I dont know what could be in my genes, at least I do have some control over my lifestyle now, and that counts for a lot, right?

Thankfully, Dr. Palaniappan assures me that family history is not the end-all, be-all of what will happen with your health.Family history is probabilistic, not predictive, she says. (Basically, it can educate you about your odds of experiencing a certain health outcome, but not predict it outright.) But if you do have access to that information, use it, since family history provides important clues about your health risks, says Dr. Palaniappan.

So if you dont have access to this information, should you be worried? And what else can you do, besides actually going out to try to find your biological relatives information (which is a hugely personal choice, and not possible for some)? There are some other things you can do to help you gather more information about your health and feel more empowered about your future.

Honestly, I didnt think about my family health history too much until I started approaching 30. As the mystery surrounding family health information came up a bit more for me, I talked to my mom and my sister about my concerns surrounding what we dont know. When my mom got me a 23andMe DNA test (which start at $199 for the Health + Ancestry test) for Christmas one year, I was excitedand kind of anxiousto have the chance to take a deeper look into my health information.

23andMe is just one example of a direct-to-consumer (DTC) DNA test that can give you some more information about your health. According to the companys website, the health reports available with the test include genetic information that can clue you in to your genetic risk for conditions like type 2 diabetes, select variants of BRCA1/BRCA2 (the gene associated with breast, ovarian, and pancreatic cancer), celiac disease, uterine fibroids, and more. The brands test can tell you about your carrier status (meaning if you carry genes linked to an inherited disease that could affect your children) for some diseases like cystic fibrosis and sickle cell anemia.

However, these DTC tests dont often come with specific consultation to walk you through whats present in your genome and how that translates into actual risk. Thats why its important to work with a genetics expert or genetic counselor if you can, says Robert C. Green MD, a medical geneticist who leads the Preventative Genomics Clinic at the Harvard-affiliated Brigham and Womens Hospital, and is the director of the Genomes2People Research Program.You [can] have a geneticist or genetic counselor who basically talks to you about what [the test results] mean and what should you do about it. What should you worry about and what should you not worry about, says Dr. Green. For example, if you tested positive for the gene for a certain hereditary cancer, a genetic counselor can help you with the next steps, like if you should seek more testing or work with a specialist.

Dr. Green adds that DTC tests arent the most comprehensive testing option. Thats because most of them use whats called chip-based DNA technology, which essentially scan your genome for known common mutations or markers along your genome, he says. [This technology] can be very good for ancestry for [finding relatives] and for certain specific markers, such as the Ashkenazi Jewish BRCA1 mutation that 23andMe looks for. It does not look at every letter in your genes, and its not typically set up to find rare or novel mutations that can affect your health. (Theyre not always super accurate, eithera 2019 study found that these chips have a very high false-positive rate for rare genetic mutations.) For health reasons sequencingwhich looks at every letter in a segment of your genome or across the whole genomeis more expensive, but much, much more comprehensive, he says.

DNA testing is definitely not cheap (it can run anywhere from $200 up to $2,000 for the more in-depth testing, and isnt always covered by insurance) and its certainly not the only way to find out more information about your health.

If you dont know much about your family health history, Dr. Palaniappan encourages paying attention to key health markers including blood pressure, cholesterol, glucose, and heart rate, and getting those checked regularly. These measurable risk factors can be effectively treated to reduce your risk of heart disease, stroke and diabetes, says Dr. Palaniappan. Everyone can reduce the risk of disease by eating a healthy diet, getting enough exercise, and not smoking. Cancer screening tests such as mammograms and colorectal cancer screening can detect precancer and treatable cancers early, she says.

While getting the DNA test felt like a great first step to knowing more about my health, its also good to know that the everyday things that I sometimes dont even think about (like walking my dog) might have a bigger impact on my health than I thought before.What you do each and every daywhat you eat, how much you exercise, and your other health behaviors, can ultimately affect your risk of developing disease, says Dr. Palaniappan. If anything, Ive learned that not knowing your family health history doesnt have to be a huge blank spot, but if I ever do want to know more, there are optionswhich is empowering for sure.

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Im 28 and I Dont Know My Family HistoryHeres How That Affects My Health - Well+Good

The changes brought by the COVID-19 pandemic have had an impact across society, and courts and IP offices are no exception. As part of our series of articles looking at what to expect in 2021, Kilburn & Strode attorneys discuss some of the legal developments on the horizon.

Its not just business meetings, webinars and Christmas quizzes that are suited to Zoom; court and IP office hearings are increasingly conducted virtually too.

At the EPO, oral proceedings in examination and oppositions will be heldonlineunless there are exceptional circumstances until September 2021 (at least). Board of Appeal hearings are heading the same way. While some practitioners have been sceptical about these changes, at Kilburn & Strode we see video conferencing as a hugely powerful and accessible medium for getting to a good decision quickly.

This is good news for SMEs, who may now be able to afford to fight cases they couldnt otherwise, says associate Rosie Carrie. But, she adds, the long-term implications are hard to predict: Will parties be more likely to be confrontational when not seeing each other in person? Will they pursue arguments more strongly? Will the opportunity to resolve issues in an informal setting be missed?

At the EUIPO, there may be changes too. Areformin 2019 overlooked by many people at the time means that the CJEU now accepts appeals from the EU General Court only where they raise an issue that is significant with respect to the unity, consistency or development of EU law. In practice, this means the General Court is now the final arbiter for most cases involving EU trade marks and registered Community designs. That may lead to the EUIPO Boards of Appeal holding more oral hearings between parties, something that until now has been extremely rare.

Patent priorities

With normal routines disrupted and the opportunity to reflect, the pandemic has led many people to consider their values and priorities getting fit, learning new hobbies or their social and political values. Policy debates about the balance between competition and innovation, between access and reward; or between control and free speech have always been part of IP. In this new environment, will we see them become even more prominent?

In patents, for example, partnerNick Bassilsays he increasingly sees morality issues being raised regarding patents for stem cells, gene therapy etc, arising from the ordre public (public policy) and morality exception in Article 53(a) of the EPC: This will become more and more relevant with genetic medicine. More generally, debates about access to medicine, the role of patents, pricing mechanisms and sourcing of drugs are gaining attention as the pandemic increases awareness (if not understanding) of the role of medicine (see our separate article on political and social trends).

On your marks

In trade marks, meanwhile, debates are continuing about the proper scope of protection and whether making broad and/or multiple related trade mark applications should be discouraged (including on the grounds of bad faith). These issues were not fully resolved in last yearsSkyKickdecision from the CJEU, but should be addressed further in the MONOPOLY case pending before the EU General Court.

Trade mark partnerIain Stewartsays: These debates reflect wider concerns about the cluttering of trade mark registers. One view is that unlike in the US where there are strict use requirements, in Europe there are too many marks that are registered but not used. It means clearance searches in the EU are becoming a nightmare. Sometimes the results run to dozens of pages, explains Iain. As well as being a practical challenge for those seeking to apply for trade marks, particularly internationally, cluttering raises questions about the accessibility of the trade mark system and its ability to serve all users, especially SMEs.

UPC or not UPC?

The end of 2020 saw Germany take important steps towards ratifying the Unified Patent Court (UPC) Agreement, raising the possibility that it could theoretically come into effect, though significant legal challenges remain (meaning ratification by Germany and implementation in 2021 is unlikely).Gwilym Robertssays: The UPC was always a lofty ideal and the simplification it offers remains attractive. But with the continuing legal challenges it faces one wonders if its time to look at alternative multilateral arrangements bringing the same benefits.Whatever comes out Kilburn & Strode will continue to be a part of it as we continue to expand our European presence.

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How the law will change in 2021 - Lexology

DALLAS--(BUSINESS WIRE)--Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a patient-centric, clinical-stage gene therapy company focused on developing and commercializing AAV-based gene therapies for the treatment of monogenic diseases of the central nervous system (CNS) in both rare and large patient populations, today announced multi-year collaborations with Cleveland Clinic and UT Southwestern Gene Therapy Program (UTSW) to advance next-generation mini-gene payloads for AAV gene therapies for the treatment of genetic epilepsies and additional CNS disorders. Taysha will have an exclusive option on new payloads, constructs and intellectual property associated with, and arising from, the research conducted under this agreement.

A team of researchers from Cleveland Clinic Lerner Research Institute will create mini-gene payloads designed to address some of the long-standing limitations in AAV gene therapy. UTSW will create and evaluate vector constructs in in vivo and in vitro efficacy models of genetic epilepsies and additional CNS disorders.

By pushing the boundaries of AAV vector engineering, we may be able to overcome some of the challenges inherent with gene therapy and potentially expand the range of treatable genetic CNS diseases with gene therapies. We appreciate the support from Taysha and UTSW in this work, said Dennis Lal, Ph.D., Assistant Staff at Cleveland Clinic Genomic Medicine Institute and Neurological Institute. We believe that our proprietary approach to overcoming current limitations of packaging capacity and our access to data on thousands of protein structures associated with a whole host of monogenic CNS disorders has the potential to enable a deep pipeline of functioning mini-genes.

Cleveland Clinic and UTSW are two of the worlds preeminent leaders in gene therapy innovation, and this collaboration is designed to leverage our capabilities and synergies with these institutions to pioneer novel approaches to address vector capacity, which is a common limitation when treating genetic disorders associated with large proteins, said Suyash Prasad, MBBS, M.SC., MRCP, MRCPCH, FFPM, Chief Medical Officer and Head of Research and Development of Taysha. We look forward to a productive collaboration with the goal of developing treatments with promising benefits to patients with debilitating genetic epilepsies.

About Taysha Gene Therapies

Taysha Gene Therapies (Nasdaq: TSHA) is on a mission to eradicate monogenic CNS disease. With a singular focus on developing curative medicines, we aim to rapidly translate our treatments from bench to bedside. We have combined our teams proven experience in gene therapy drug development and commercialization with the world-class UT Southwestern Gene Therapy Program to build an extensive, AAV gene therapy pipeline focused on both rare and large-market indications. Together, we leverage our fully integrated platforman engine for potential new cureswith a goal of dramatically improving patients lives. More information is available at http://www.tayshagtx.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as anticipates, believes, expects, intends, projects, and future or similar expressions are intended to identify forward-looking statements. Forward-looking statements include statements concerning or implying the potential of our collaboration with the Cleveland Clinic and UTSW, the potential of our product candidates to positively impact quality of life and alter the course of disease in the patients we seek to treat, our research, development and regulatory plans for our product candidates, the potential benefits of rare pediatric disease designation and orphan drug designation to our product candidates, the potential for these product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies, and whether, if approved, these product candidates will be successfully distributed and marketed. Forward-looking statements are based on managements current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. Risks regarding our business are described in detail in our Securities and Exchange Commission (SEC) filings, including in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, which is available on the SECs website at http://www.sec.gov. Additional information will be made available in other filings that we make from time to time with the SEC. Such risks may be amplified by the impacts of the COVID-19 pandemic. These forward-looking statements speak only as of the date hereof, and we disclaim any obligation to update these statements except as may be required by law.

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Taysha Gene Therapies Announces Collaborations to Advance Next-Generation Mini-Gene Payloads for AAV Gene Therapies for the Treatment of Genetic...