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Category Archives: Gene Medicine

Significant Positive Shift in the Cell and Gene Therapies in Rare … – PR Newswire

The dynamics of the cell and gene therapies market in rare disorders are anticipated to change as companies across the globe are thoroughly working toward developing new therapeutic options to treat a wide array of indications.

LAS VEGAS, May 9, 2023 /PRNewswire/ --DelveInsight's Cell and Gene Therapies in Rare Disorders Market Insights report includes a comprehensive understanding of current treatment practices, emerging cell and gene therapies for various rare disorders, market share of individual therapies, and current and forecasted market size from 2019 to 2032, segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan].

Key Takeaways from the Cell and Gene Therapies in Rare Disorders Market Report

Discover which therapies are expected to grab the major cell and gene therapies in rare disorders market share @ Cell and Gene Therapies in Rare Disorders Market Report

Cell and Gene Therapies in Rare Disorders Overview

Cell and gene therapies use genes and cells to treat disease. A gene is a unit of DNA containing genetic information passed down from generation to generation. The genome comprises all genes; genes may contain information on observable features such as height or eye color. Many genes contain instructions for RNA or protein molecules that are not visible from the outside but serve crucial tasks in the body's cells. Cells are the building blocks of plants and animals (including humans); they are small functional units that work together to generate organs and tissues. Cell and gene therapy technology is quickly evolving for many different diseases. However, cell and gene treatments are still experimental drugs, and much more study is required before many of these therapies are available to patients worldwide.

Cell and Gene Therapies in Rare Disorders Epidemiology Segmentation

DelveInsight estimates that there were approximately 900K prevalent cases of selected indications for cell and gene therapies in rare disorders in the 7MM in 2022.

As per our analysis, the highest prevalent cases from the selected indications for cell and gene therapies in rare disorders were for Retinitis Pigmentosa in the United States, whereas the least cases were reported for Hunter Syndrome in 2022.

The cell and gene therapies in rare disorders market reportproffers epidemiological analysis for the study period 20192032 in the 7MM segmented into:

Cell and Gene Therapies in Rare Disorders Market Insights

Numerous cell and gene therapies for rare diseases are currently approved in the 7MM, including retinitis pigmentosa (LUXTURNA), beta-thalassemia (ZYNTEGLO), epidermolysis bullosa (JACE), limbal stem cell deficiency (OCURAL), and many others. As per Delveinsight analysis, the total cell and gene therapies in rare disorders market size was around USD 1.5 billion in 2022. According to predictions, the United States will have the largest cell and gene therapies in rare disorders market. ZOLGENSMA produced the highest revenue of roughly USD 1 billion among the 7MM in 2022, while ROCTAVIAN is predicted to take the highest market share by 2032. ROCTAVIAN has received conditional approval in Europe for the treatment of severe hemophilia A. In addition to this approval, BioMarin Pharmaceutical is working to approve the drug in the United States, with a PDUFA target action date of June 30, 2023.

Hemophilia A is predicted to produce the most revenue among the selected indications by 2032, owing to the precedence of existing high treatment cost and expected high cost for emerging therapies along with significant residual unmet need. Gene treatments for Hemophilia A are estimated to earn around USD 6 billion in sales revenue by 2032 in the 7MM. The field of cell and gene therapies for rare indications is expected to rapidly expand in the coming years, as an increasing number of companies submit investigational new drug applications for these treatments each year, along with rising regulatory approval in the United States and Europe. In terms of manufacturing aspects of cell and gene therapies, there will be more competition for contract manufacturing businesses and pharmaceutical/biotechnology firms. The competition for contract manufacturing organization's production capacity will intensify as more companies enter the cell and gene therapy market, possibly driving up manufacturing costs. To ensure pharmaceutical/biotechnology firms can compete or obtain an advantage over competitors, companies may need to invest in manufacturing technologies or acquire companies with manufacturing expertise.

To know more about cell and gene therapies in rare disorders treatment guidelines, visit @ Cell and Gene Therapy Insights

Emerging Cell and Gene Therapies for Hemophilia A and Key Companies

Emerging Cell and Gene Therapies for Hemophilia B and Key Companies

Emerging Cell and Gene Therapies for Fabry Disease and Key Companies

Emerging Cell and Gene Therapies for Pompe Disease and Key Companies

Emerging Cell and Gene Therapies for Leber Hereditary Optic Neuropathy and Key Companies

Emerging Cell and Gene Therapies for Retinitis Pigmentosa and Key Companies

Emerging Cell and Gene Therapies for Hunter Syndrome and Key Companies

Emerging Cell and Gene Therapies for Batten Disease and Key Companies

Emerging Cell and Gene Therapies for Duchenne Muscular Dystrophy (DMD) and Key Companies

Emerging Cell and Gene Therapies for Amyotrophic Lateral Sclerosis (ALS) and Key Companies

Emerging Cell and Gene Therapies for Beta Thalassemia and Sickle Cell Anemia and Key Companies

Emerging Cell and Gene Therapies for Dystrophic Epidermolysis Bullosa and Key Companies

Emerging Cell and Gene Therapies for Ornithine Transcarbamylase Deficiency and Key Companies

Emerging Cell and Gene Therapies for Sanfilippo Syndrome Type A and Key Companies

Emerging Cell and Gene Therapies for Glycogen Storage Disease Type IA and Key Companies

Learn more about the FDA-approved cell and gene therapies for rare disorders @ Approved Cell and Gene Therapies in Rare Disorders Treatment

Cell and Gene Therapies in Rare Disorders Market Dynamics

The cell and gene therapies in rare disorders market is predicted to grow positively due to an increase in the approval of a growing number of gene therapies and their ease of adoption following approval, the ability to treat a wide range of conditions, an increase in the number of cases, an expected one-time dosing approach, and curative treatment options.

The approval of LIBMELDY, SKYSONA, HOLOCLAR, UPSTAZA, ROCTAVIAN, and other medicines has successfully created regulatory channels for the development of further cell and gene therapies. Companies around the world are working hard to develop new cell and gene therapies options to treat a wide range of indications, such as hemophilia A and B, lysosomal storage disorder (Fabry, Pompe Disease, Danon Disease, MPS I, MPS II, MPS III), neurological disorders (Batten, Parkinson), musculoskeletal disorders (DMD, myotubular myopathy), eye diseases (achromatopsia, limbal stem cell deficiency, retinitis pigmentosa, retinoschisis, age-related macular degeneration, Leber's hereditary optic neuropathy), and other indications such as diabetic macular edema, inborn metabolism disorder (Wilson's disease, Phenylketonuria, OTC deficiency/urea cycle disorders), dystrophic epidermolysis bullosa, gangliosidosis, and xerostomia.

Many diseases' treatment landscapes have drastically evolved in the last few years. Companies are now developing cell and gene therapies that will play an important role in the future, particularly in the treatment of rare genetic disorders. The process of defining ideal candidates for given gene therapy and cell therapy will have to wait for the enrolment and long-term follow-up of a sufficient number of study subjects to provide satisfactory clarity regarding its safety and efficacy. In conclusion, the future of cell and gene therapy looks optimistic. Several clinical trials have yielded favorable results in terms of safety and efficacy. The findings of these studies motivate additional research into many indications, and the current scenario predicts a positive shift in the cell and gene therapies in rare disorders market for the forecast period.

However, several factors may impede the growth of cell and gene therapies in rare disorders market in the coming years. Despite advances since the enactment of the Orphan Drug Act, people in the United States with rare diseases continue to face challenges to diagnosis, care, and treatment. Moreover, in Europe, a possible crisis with gene treatments for rare diseases is developing, and few companies have withdrawn the drug after failing to get reimbursement in the EU.

Report Metrics

Details

Study Period

20192032

Coverage

7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]

Base Year

2019

Cell and Gene Therapies in Rare Disorders Market CAGR

35.8%

Cell and Gene Therapies in Rare Disorders Market Size in 2022

USD 1.5 Billion

Key Cell and Gene Therapies in Rare Disorders Companies

Roche, Freeline Therapeutics, Spark Therapeutics, Astellas Gene Therapies, Actus Therapeutics, GenSight Biologics, Coave Therapeutics, Johnson & Johnson, MeiraGTx, Applied Genetic Technologies Corporation, GenSight Biologics, Nanoscope Therapeutics, 4D Molecular Therapeutics, Ocugen, jCyte, ReNeuron, REGENXBIO, Amicus Therapeutics, Pfizer, Sarepta Therapeutics, Capricor Therapeutics, Nippon Shinyaku, Brainstorm Cell Therapeutics, CRISPR Therapeutics, Vertex Pharmaceuticals, Editas Medicine, Sangamo Therapeutics, Krystal Biotech, Abeona Therapeutics, Castle Creek Biosciences, Holostem Terapie Avanzate S.r.l., RHEACELL, Ishin Pharma, Anterogen, Ultragenyx Pharmaceutical, and others

Key Pipeline Cell and Gene Therapies in Rare Disorders Therapies

Giroctocogene fitelparvovec, Dirloctocogene samoparvovec, Fidanacogene elaparvovec, Verbrinacogene setparvovec (FLT-180a), FLT190, Isaralgagene civaparvovec (ST-920), 4D-310, SPK-3006, AT845, ACTUS-101, LUMEVOQ (lenadogene nolparvovec), CTx-PDE6b, Botaretigene sparoparvovec, ATGC-501 (laruparetigene zosaparvovec), GS030, MCO-010 (sonpiretigene isteparvovec), 4D-125, OCU400, jCell, RGX-121, AT-GTX-502 (scAAV9.P546.CLN3), PF-06939926, SRP-9001, CAP-1002, NurOwn (MSC-NTF cells), Exagamglogene autotemcel, EDIT-301, BIVV003, VYJUVEK (beremagene geperpavec), EB-101, D-Fi (dabocemagene autoficel), RV-LAMB3-transduced epidermal stem cells, Allogeneic ABCB5-positive Stem Cells, ISN001, ALLO-ASC-SHEET, DTX301, UX111 (ABO-102), DTX401 (AAV8G6PC), and others

Scope of the Cell and Gene Therapies in Rare Disorders Market Report

Discover more about cell and gene therapies for rare disorders in development @ Cell and Gene Therapy Clinical Trials

Table of Contents

1

Cell and Gene Therapies in Rare Disorders Market Key Insights

2

Cell and Gene Therapies in Rare Disorders Market Report Introduction

3

Cell and Gene Therapies in Rare Disorders Market Key Highlights from Report

4

Executive Summary of Cell and Gene Therapies in Rare Disorders

5

Key Events: Cell and Gene Therapies in Rare Disorders

6

Cell and Gene Therapies in Rare Disorders Epidemiology and Market Forecast Methodology

7

Cell and Gene Therapies in Rare Disorders Market Overview at a Glance in the 7MM

8

Disease Background and Overview of Cell and Gene Therapies in Rare Disorders

9

Epidemiology and Patient Population

10

Marketed Cell and Gene Therapies in Rare Disorders

10.1

Key Competitors in Cell and Gene Therapies in Rare Disorders

10.2

Hemophilia A

10.2.1

ROCTAVIAN (valoctocogene roxaparvovec): BioMarin Pharmaceutical

10.3

Hemophilia B

10.3.1

HEMGENIX (etranacogene dezaparvovec): CSL Behring/uniQure

10.4

Retinitis Pigmentosa

10.4.1

LUXTURNA: Sparks Therapeutics (a company of Roche)/ Novartis

10.5

Spinal Muscular Atrophy (SMA)

10.5.1

ZOLGENSMA (onasemnogene abeparvovec-xioi): Novartis (AveXis)

10.6

Metachromatic Leukodystrophy (MLD)

10.6.1

LIBMELDY (atidarsagene autotemcel): Orchard Therapeutics

10.7

Limbal Stem Cell Deficiency

10.7.1

HOLOCLAR (Autologous human corneal epithelial cells containing stem cells): Holostem Terapie Avanzate S.r.l.

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Significant Positive Shift in the Cell and Gene Therapies in Rare ... - PR Newswire

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Endovascular Thrombectomy Shows Better Functional Outcomes … – Neurology Live

Recently published in The New England Journal of Medicine, new findings from the SELECT2 trial (NCT03876457), a phase 3 international, randomized, open-label clinical trial, showed endovascular thrombectomy (EVT) resulted in better functional outcomes than medical care among patients with large ischemic strokes 24 hours after onset.1 These results provide evidence of the efficacy and safety of endovascular thrombectomy in patients with large ischemic strokes, which has been carried out in limited populations to date.

In favor of EVT, the generalized odds ratio for a shift in the distribution of modified Rankin scale (mRS) scores toward better outcomes was 1.51 (95% CI, 1.20-1.89; P <.001). Notably, a total of 20% of the patients in the EVT group and 7% in the medical-care group had functional independence (RR, 2.97; 95% CI, 1.60-5.51).

These findings were also presented as an oral presentation in the clinical trials plenary session at the 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27, in Boston, Massachusetts, by lead author Amrou Sarraj, MD, director of the Cerebrovascular Center and Comprehensive Stroke Center at University Hospitals Cleveland Medical Center. The session covered the latest clinical trial results that impact the landscape of patient care in all the neurology subspecialities.2

Between September 2019 and September 2022, at the time the trial was stopped, 958 patients had been screened, and among those, 352 were eligible and enrolled. The trial included patients with stroke because of occlusion of the internal carotid artery or the first segment of the middle cerebral artery, and assessed EVT in the time span of 24 hours after onset. The patients enrolled had a large ischemic-core volume, defined by the Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0- 10, with lower scores indicating larger infarction) or at least 50 mL of a core volume on computed tomography perfusion or diffusion-weighted MRI.

Patients were assigned on a 1:1 ratio to either the EVT plus medical care group (n = 178) or the medical care alone group (n = 174). The mRS score at 90 days (range, 0-6, with higher scores indicating greater disability) was the primary outcome, and functional independence was the secondary outcome.

Among both groups, mortality was similar. Arterial access-site complications occurred in 5 patients, dissection in 10 patients, cerebral-vessel perforation in 7 patients, and transient vasospasm in 11 patients, all of whom were in the EVT group. One patient in the EVT group and 2 patients in the medical-care group experienced symptomatic intracranial hemorrhage.

Limitations of the trial include its early termination and the smaller than anticipated sample size. Although treatment was open label, the outcome assessment was conducted by assessors who were unaware of trial-group assignments. In addition, some patients enrolled had lower ischemic-core volumes than intended for enrollment and only approximately 20% of patients received intravenous thrombolytic agents before randomization.

Previous coverage of SELECT2 identified no safety concerns during a review of 90-day outcomes for the first 200 included participants.3 Findings from that analysis were presented at the 2022 International Stroke Conference (ISC) February 9-11, in New Orleans, Louisiana, by Sarraj. In the analysis, 200 patients were enrolled in the phase 3 study, 100 patients randomized received EVT and 100 were randomized to medical management (MM).

In the data presented at ISC 2023, participants in the EVT group had a median age of 66.5 years (IQR, 58.5-75) and those in the MM group had a median age of 67.5 (IQR, 59-76). Presentation National Institutes of Health Stroke Scale (NIHSS) scores were similar, averaging 19 (IQR, 15-23) for the EVT group and 19 (IQR, 15-23) in the MM group, as was time from stroke onset to randomization, averaging 9.3 hours (IQR, 5.0-15.25) for the EVT group and 9.9 hours (IQR, 5.95-15.9) for the MM group, and physician read CV Alberta Stroke Program Early CT Scores (ASPECTS), at 4 (IQR, 4-5) for the EVT group and 4 (IQR, 4-5) for the MM group. Overall, 176 patients had NCCT ASPECTS between 3-5, with a median ischemic core of 72 mL (IQR, 38.5-108.5). A total of 145 patients had an ischemic core of 50 mL, with a median ischemic core of 94 (IQR, 72-138).

Click here for more coverage of AAN 2023.

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People on the Move: May 12 – Delaware Business Times

People on the Move is a rundown of recent hirings, promotions, appointments and other notable movements by professionals in the state. If youre interested in submitting an entry, please contact news@delawarebusinesstimes.com.

U.S. Senator Tom Carper (D-Del.) was named to the National Advisory Board for President Joe Bidens re-election campaign. The National Advisory Board is a select group of national Democratic leaders who will serve as the primary surrogates for the Democratic National Committee and Biden-Harris campaign in 2023 and 2024.

U.S. Senator Tom Carper (D-Delaware)

Im excited to join President Bidens national advisory board to stand beside my good friend Joe throughout his re-election campaign. Since they took office, President Biden and Vice President Harris have been fighting for everyday Americans and to protect our freedoms,Senator Tom Carper said in a statement. President Biden ran for the presidency in 2020 because he believed that we were in a battle for the soul of this nation and we still are. I encourage all Delawareans to join me in supporting the Biden-Harris campaign so we can all come together to help Joe and Kamala finish the job.

The stakes of this election couldnt be higher, President Joe Biden said. Our freedom and democracy are on the line. Im grateful to this group of diverse and dynamic leaders who will help us win the battle for the soul of America and finish the job for the American people.

Gawthrop Greenwood partner Carl W. Heckert has been elected secretary of the Delaware State Bar Associations Family Law Section during the esteemed organizations 100th anniversary year.

Heckert, who has more than 25 years of experiencepracticing family law in Delaware, has been a member of the Delaware State Bar Association since 1992 and will serve for the 2023-2024 section year.

Carl Heckert | PHOTO COURTESY OF GAWTHROP

Heckert is a member of theFamily Law Departmentin Gawthrop Greenwood, PCs Greater Wilmington office in Greenville, litigating and mediating divorce. In 2019, he became a Certified Family Law Mediator in Delaware following the states inaugural certification program by the Family Court of the State of Delaware as well as the Delaware State Bar Association. A certified Delaware family law mediator is a neutral third party who is charged with preserving confidentiality while helping couples resolve issues more creatively and amicably than they can in court, including custody, visitation, child support, property division and alimony.

Heckert also draws on his more than 30 years of real estate experience to settle real estate disputes during divorce proceedings. In January, he presented a seminar on the topic for Delaware family law judges and practitioners of theMelson-Arsht Inns of Court. He has also led Continuing Legal Education courses in family law matters including custody, protection from abuse and representing an unwilling minor as a guardian-ad-litem. Heckert received his law degree fromWidener University School of Lawand holds a Bachelor of Science degree from theUniversity of Delaware.

Wilmington Trust announced the addition ofSuzanne Lane as the senior relationship executive.

Lane will focus on asset managers and financial institution relationships for the loan market solutions team, employing innovative solutions to help meet individual clients goals. Throughout her 25-year career in corporate trust and banking, she has taken numerous leadership positions on multiple finance and asset management teams.

Lane is a passionate advocate about empowering women in the financial services industry and has served as a mentor for many women as they start or build their careers. Prior to joining Wilmington Trust, Lane was a relationship lead for U.S. Banks Global Platinum Corporate Trust clientele.Previously, she was Chief of Staff for Relationship Management in the Shareowner Services division of BNY Mellon. She also has held roles at KPMG, AIB, and State Street Bank.

Lane has managed large client service teams both domestically and in Europe. She holds a bachelors degree in business administration from Northeastern University, and has earned the CPA, CFA and CAIA designations.

Allen Friedland, M.D., MACP, FAAP, has been recognized with the Dema C. Daley Founders Award for his national impact as an educator, innovator and leader in internal medicine.

Allen Friedland | PHOTO COURTESY OF CHRISTIANACARE

Given by the Alliance for Academic Internal Medicine, the award honors internal medicine doctors who have greatly influenced undergraduate and graduate medical education and the development of training programs in internal medicine.

Dr. Friedland has been a tireless advocate and innovator for internal medicine, medicine-pediatrics, and residency education over two decades, said Vinay Maheshwari, M.D., MHCDS, Hugh R. Sharp Jr., Chair of Medicine and physician executive of the Medical Group at ChristianaCare. He is a mentor to countless physicians across the country and beloved by those who have had the privilege of working alongside him. What is most evident about Dr. Friedland is how much he cares about those he has taught locally and nationally all of them will forever be a part of his family. This award is a testament to a lifetime career dedicated to graduate medical education.

Friedland is ChristianaCares section chief of Medicine-Pediatrics (Med-Peds) and has served as the director of ChristianaCares combined Internal Medicine-Pediatrics residency program for 25 years. He also teaches medical students at ChristianaCare, which is a branch campus of Sidney Kimmel Medical College at Thomas Jefferson University and Philadelphia College of Osteopathic Medicine.

His accomplishments include:

Amanda Hewes, MS, education program manager at ChristianaCares Gene Editing Institute, has been named one of the 2023 Outstanding Delaware Women in STEM by Million Women Mentors, an international movement dedicated to encouraging girls and women to pursue careers in science, technology, engineering and math (STEM).

Amanda Hewes | PHOTO COURTESY OF CHRISTIANACARE

Hewes selection spotlights her dedication to engaging young people in the science of gene editing by introducing the Gene Editing Institutes CRISPR in a BoxTM educational toolkit into classrooms across Delaware and her commitment to bridging disparities in STEM education.

Im overjoyed to be honored among so many amazing women in this state, Hewes said. Its humbling to be considered and to stand alongside them. All of these women foster and lead dynamic communities of young women that inspire me every day. I hope that I can do the same by making young women in this state feel empowered through the work that I do.

Hewes joined ChristianaCares Gene Editing Institute in 2017 with a focus on expanding its CRISPR gene editing system in a cell-free environment. She was first author in a publication in Nature that established the highly innovative gene editing on a chip protocol that allowed CRISPR to edit DNA outside of the cell for the first time. This methodology enables researchers to take fragments of DNA extracted from human cells, place them in a test tube and precisely engineer multiple changes to the genetic code.

This gene editing system eventually led to the creation of the CRISPR in a Box toolkit. This innovative educational resource provides a way for students to learn about this exciting frontier of science through a hands-on exercise in which they use CRISPR gene editing to disrupt a synthetic gene within a plasmid. The simplicity of this experiment allowed for the reaction to be developed into a remarkable teaching tool that can be brought into most school laboratories containing basic laboratory equipment.

Once CRISPR in a Box was developed, Hewes recognized the potential it could have for high school and college students. She took on a new role as education program manager and expanded the Gene Editing 360 platform, which is the Gene Editing Institutes suite of educational tools for engaging students and the public.

Hewes was honored alongside 10 other women by Gov. John Carney, Lt. Gov. Bethany Hall-Long and others at the Delaware State House with the signing of a proclamation to declare March 24, 2023, as Delaware Women and Girls in STEM Day.

After 35 years of wearing Service Unlimited, Inc. (SUI) green, Safety Coordinator David Parag announced his retirement closing out a remarkable career serving the company and the people of New Castle, Delaware, and the surrounding areas.

Originally hired in the mid-1970s as an HVAC mechanic, Parag has served our customers in many different roles over three different terms. In his second term with the SUI family, Parag served as an electrician for our sister company, Electric Unlimited, Inc. (EUI), and ultimately led the company. Parag again returned to SUI as the Director of Construction Quality. He eventually added safety responsibilities to that role. Parag most recently was Safety Coordinator because of his passion for doing things the safest way rather than the fastest or easiest way.

Parag holds a Master License in both HVAC and Electrical. He has conducted countless training sessions, delivered tons of how-to documents, and mentored dozens of team members including Vice President Brian Martinenza. Parag will always be known around SUI for his oversized brain and his oversized heart because he knows virtually everything, and cares deeply about the people in his life. He enjoys being a catalyst for personal development and professional growth.

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People on the Move: May 12 - Delaware Business Times

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Brain-belly connection: gut health may influence likelihood of … – EurekAlert

image:A UNLV researcher holds a human brain model. view more

Credit: Josh Hawkins/UNLV

Could changing your diet play a role in slowing or even preventing the development of dementia? Were one step closer to finding out, thanks to a new UNLV study that bolsters the long-suspected link between gut health and Alzheimers disease.

The analysis led by a team of researchers with the Nevada Institute of Personalized Medicine (NIPM) at UNLV and published this spring in the Nature journalScientific Reports examined data from dozens of past studies into the belly-brain connection. The results? Theres a strong link between particular kinds of gut bacteria and Alzheimers disease.

Between 500 and 1,000 species of bacteria exist in the human gut at any one time, and the amount and diversity of these microorganisms can be influenced by genetics and diet.

The UNLV teams analysis found a significant correlation between 10 specific types of gut bacteria and the likelihood of developing Alzheimers disease. Six categories of bacteria Adlercreutzia, Eubacterium nodatum group, Eisenbergiella, Eubacterium fissicatena group, Gordonibacter,andPrevotella9 were identified as protective, and four types of bacteria Collinsella, Bacteroides, Lachnospira,andVeillonella were identified as a risk factor for Alzheimers disease.

Certain bacteria in humans guts can secrete acids and toxins that thin and seep through the intestinal lining, interact with theAPOE(a gene identified as a major risk factor for Alzheimers disease), and trigger a neuroinflammatory response affecting brain health and numerous immune functions, and potentially promoting development of the neurodegenerative disorder.

Researchers said their novel discovery of the distinct bacterial groups associated with Alzheimers disease provides new insights into the relationship between gut microbiota and the worlds most common form of dementia. The findings also advance scientists understanding of how an imbalance of that bacteria may play a role in the disorders development.

Most of the microorganisms in our intestines are considered good bacteria that promote health, but an imbalance of those bacteria can be toxic to a persons immune system and linked to various diseases, such as depression, heart disease, cancer, and Alzheimers disease, said UNLV research professorJingchun Chen. The take-home message here is that your genes not only determine whether you have a risk for a disease, but they can also influence the abundance of bacteria in your gut.

While their analysis established overarching categories of bacteria typically associated with Alzheimers disease, the UNLV team said further research is needed to drill down into the specific bacterial species that influence risk or protection.

The hope is to one day develop treatments that are customized for an individual patient and their genetic makeup, such as medications or lifestyle change. Studies have shown that changes in gut microbiome through probiotic use and dietary adjustments can positively impact the immune system, inflammation, and even brain function.

With more research it would be possible to identify a genetic trajectory that could point to a gut microbiome that would be more or less prone to developing diseases such as Alzheimers, said study lead author and UNLV graduate student Davis Cammann, but we also have to remember that the gut biome is influenced by many factors including lifestyle and diet.

Genetic correlations between Alzheimers disease and gut microbiome generawas published this spring inScientific Reports.

In addition to faculty, undergraduate, and graduate student researchers from NIPM, scientists from the UNLV College of Sciences, UNLV School of Dental Medicine, UNLV School of Integrated Health Sciences Department of Brain Health, Kirk Kerkorian School of Medicine at UNLV, Columbia University, and University of Texas Health Science Center at Houston contributed to the study.

Scientific Reports

Meta-analysis

Cells

Genetic correlations between Alzheimers disease and gut microbiome genera

31-Mar-2023

The authors declare no competing interests.

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

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St. Jude scientist M. Madan Babu elected to the Royal Society of … – St. Jude Children’s Research Hospital

St. Jude Childrens Research Hospital scientist Madan Babu Mohan, Ph.D., Center of Excellence in Data-Driven Discovery director and member of the Department of Structural Biology, has been elected a Fellow of the Royal Society of London. The Royal Society is the oldest scientific academy in continuous existence.

Babu was selected to join the Royal Society for his pioneering data science-based strategies to reveal fundamental principles in biological systems. His scientific accomplishments include determining the molecular mechanisms governing G-protein-coupled receptor (GPCR) signaling, uncovering the roles of disordered protein regions in biology and disease, and establishing genome-scale principles of gene regulation.

One-third of all Food and Drug Administration-approved drugs target GPCRs, membrane proteins found on the surface of cells. Babus work has shown how genetic and isoform variability of GPCRs can influence drug responses. His most recent work investigated how GPCR selectivity for G-proteins is determined. Understanding this family of proteins is of tremendous interest to the development of novel therapeutics.

I am honored for our work to receive this recognition, Babu said. The science we have achieved is possible because of long-term support for fundamental research and the collaborative environment at St. Jude and the MRC Laboratory of Molecular Biology in Cambridge, England. I am grateful for the many contributions of my past and current colleagues, as well as my mentors and family.

Dr. Babus election to the Royal Society is well-earned, and we are all honored to call him a colleague, said James R. Downing, M.D., president and CEO of St. Jude. His investigations of GPCRs have the potential to have profound implications for pharmaceutical development. Through these discoveries, we can advance cures for pediatric cancer and other catastrophic diseases.

I am delighted to welcome our newest cohort of Fellows, said Sir Adrian Smith, President of the Royal Society. They are pioneering scientists and innovators from around the world who have confounded expectations and transformed our thinking.

Founded in the 1660s, the Royal Society is an independent scientific academy of the U.K. and the Commonwealth. Its Fellows have included many of the worlds most eminent scientists and technologists, representing a range of personalities, from Sir Isaac Newton and Benjamin Franklin to Dorothy Hodgkin and Robert Webster (St. Jude Infectious Diseases, emeritus).

This year sees 59 Fellows, 19 Foreign Members and two Honorary Fellows elected. Babus fellow U.S.-based new Fellows and Foreign Members include researchers at Google DeepMind, Harvard University, the Howard Hughes Medical Institute, the Institute for Advanced Study, Stanford University and the University of Chicago.

Babu joined the faculty of St. Jude in 2020, following a 14-year tenure as a program leader at the MRC Laboratory of Molecular Biology in Cambridge, England. He earned his Ph.D. in computational genomics from Cambridge University and his undergraduate degree from Anna University, Chennai, India. Babu completed a postdoctoral fellowship with the National Institutes of Health, Bethesda, Maryland.

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St. Jude scientist M. Madan Babu elected to the Royal Society of ... - St. Jude Children's Research Hospital

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Prevalence of BRCA homopolymeric indels in an ION Torrent-based … – Nature.com

Patients cohort

Among consecutive patients who underwent BRCA tumour testing through ION Torrent-based sequencing between August 2017 and February 2022, we retrospectively selected 222 high-grade ovarian cancer (HGOC) patients with the following histological subtypes: 203 serous (HGSOC), seven endometrioid, five clear-cell and seven with mixed histotypes.

Since NGS BRCA1/2 tumour testing was not available before 2017 in our Institution, 19 of 222 subjects underwent germline testing before tumour sequencing based on personal (very early age at diagnosis/previous breast cancer) or family history. According to the workflow used by our Molecular Tumour Board (MTB), in 73 out of 203 patients with upfront tumour testing subsequently received genetic counselling, either for targeted germline sequencing of a tumour-detected PV or for large genomic rearrangement analysis14.

The Ethics committee of Fondazione IRCCS Istituto Nazionale dei Tumori of Milan approved the use of both clinical and molecular data collected by the MTB for clinical studies and granted exemption from requiring written consent for tumour genetic testing from the patients, as these analyses were carried out in the context of a diagnostic and care setting (Approval Number INT 227/20). All the probands who underwent germline testing were aged over 18 and provided signed informed consent for the use of their biological samples and data for both diagnostic and research purposes. All methods were carried out in accordance with relevant guidelines and with the ethical principles of the Declaration of Helsinki.

The BRCA1 and BRCA2 genes were assessed by in-house NGS testing using the Oncomine BRCA Research Assay (Thermo Fisher Scientific, Inc). This assay provided a 100% coverage of all BRCA1 and BRCA2 exons, with an average of 64 bases of intronic flanking sequences upstream and downstream of each exon. Five m sections from formalinfixed paraffin-embedded (FFPE) samples were manually microdissected to isolate the highest percentage of neoplastic cells. Genomic DNA was extracted with protease K (incubation ON at 55C) and quantified with Qubit dsDNA BR kit (Thermo Fisher Scientific, Inc). The libraries were prepared with the IonAmpliSeq Library kit 2.0 (Thermo Fisher Scientific, Inc) and quantified with Qubit dsDNA HS kit (Thermo Fisher Scientific, Inc) following the manufacturers instructions. The libraries are diluted to 25pm, pooled and loaded on the Ion Chef to perform emulsion PCR and chip loading on 318 v2 chips. Sequencing was performed on ION PGM, using the HI-Q view Chef kit, according to the manufacturers instructions. Data were processed using the Torrent Suite 5.12.3 (TS). The quality of sequencing output was first evaluated through the plugin Coverage Analysis on the TS. Only samples whose librarys uniformity and on-target values were at least 80% and with a medium coverage of 1500X were considered valid. SNV analysis was performed in duplicate: the first variant calling was generated by the Variant Caller plugin from the TS and the resulting VCF file was loaded in the Variant Effect Predictor Tool (Ensembl, Version GRCh37) for the variants annotation. To eliminate erroneous base calling, we set each variant coverage>40X, a variant frequency on each sample>2% and a quality value>30. Variants within homopolymer (HP) longer than eight bases and with strand bias80% were not reported. In the second analysis, the BAM files were automatically uploaded from the TS to the Ion Reporter Software (IR, version 5.6 to 5.16) and the variant calling was integrated into the analysis pipeline Oncomine BRCA Research Somatic318. The results of both analyses were manually compared. Each variant was displayed on IGV (ver. 2.3.97). Synonymous variants were filtered out, while the remaining variants were classified into pathogenicity classes according to the Evidence-based Network for the Interpretation of Mutant Alleles (ENIGMA) consortium guidelines (https://enigmaconsortium.org/). Our assay could not reliably detect large intragenic rearrangements.

Two EDTA tubes of peripheral blood samples were collected from each patient who performed genetic counselling and was eligible for germline testing, either for targeted sequencing of tumour-detected pathogenic/likely pathogenic variants or for the analysis of large genomic rearrangements in patients with no actionable variants detected at tumour testing. Whole blood DNA was isolated through the MagCore Super automatic workstation with the MagCore Genomic DNA Whole Blood Kit (Diatech LabLine SRL, Jesi, Italy). Targeted Sanger sequencing of tumour-detected BRCA1/2 PVs was performed on purified PCR products by using BigDye Terminator v.3.1 Cycle Sequencing kit (Thermo Fisher Scientific, Inc.) and run on 3730Xl DNA Analyzer (Applied Biosystems; Thermo Fisher Scientific, Inc.), after purification with Agencourt CleanSeq-Beckman Coulter. Sequences were analysed by Mutation Surveyor Software (v5.0.1; SoftGenetics, LLC., State College, PA, USA). Targeted sequencing results were confirmed on both blood aliquots collected from each patient. Variants of uncertain clinical significance identified at tumour testing were not systematically investigated at the germline level. Eligible probands, who resulted negative at tumour testing with the Oncomine BRCA assay, were analysed for large deletions and duplications of BRCA1 and BRCA2 on blood DNA with the SALSA MLPA kits P045 BRCA2/CHEK2 and P002 BRCA1 probe mix (MRC-Holland, Amsterdam, the Netherlands), following the manufacturers instructions. MLPA products were run on the 3730Xl DNA Analyzer (Applied Biosystems; Thermo Fisher Scientific, Inc.) with the Gene Mapper Module (Applied Biosystems; Thermo Fisher Scientific, Inc.). The results were analysed through the Gene Marker Software v2.7.0 (SoftGenetics, LLC, State College, PA, USA).

Based on previous observations on the performance at homopolymers of ion semiconductor sequencing techniques, we focussed our analysis on stretches of six or more identical bases since the calling accuracy has been consistently shown to dramatically drop beyond this length15,17,25,28,30. We thus selected all 29 homopolymeric regions exceeding five repetitions to be analysed within the coding regions of both genes, including five in BRCA1 and 24 in BRCA2. Since truncating variants beyond codon 3326 of BRCA2 are not classified as high-risk variants, homopolymers downstream of the residue c.9976 of BRCA2 were not included in the analysis (Table 2).

To overcome the limitations of the ION reporter software, which filters out most indels at homopolymeric regions, we manually visualised the BAM alignment files of the 222 patients at the 29 regions with the IGV software (ver. 2.3.97). The median depth of coverage of the regions of interest ranged from 1045 to 6989X. Each sample showed a variable frequency of sequence alterations (both insertions and deletions) at each region. We estimated the variant allele frequency (VAF) of insertions and deletions (indels) by calculating the ratios of the maximum inserted or deleted reads over the total reads at each homopolymer (Suppl. Table 1).

Since the VAF of indels at homopolymeric regions has, in general, a left-skewed distribution, we employed a modified version of the Cancer Outlier Profile Analysis (COPA) approach31, which consists in scaling the above-cited to a normal distribution and subsequently calculating the outliers that exceeded the mean+3 median-adjusted deviations (+3) threshold.

To validate the outliers, for each of the 29 regions, we further defined a threshold based on the normalized distributions (either for percentage of insertion or deletion) of a control population. Since both in ovarian and other BRCA-associated cancers the predominant second hit is most often represented by loss of heterozygosity (LOH), while a second point mutation is an extremely rare event32,33,34, we used as control population a cohort of 46 patients in which a non-homopolymeric PV (either somatic or germline) had been already identified.

To avoid potential selection bias, which would affect the estimated frequency of pathogenic variants occurring at homopolymeric regions in our cohort, we excluded from the analysis the 19 patients who underwent germline testing before tumour testing. This group also included two patients with germline-confirmed homopolymeric PVs who resulted negative at tumour testing.

Therefore, we applied the (+3) thresholds estimated on the control population to the normalized distributions of the study cohort, composed of 157 individuals with no evidence of pathogenic variants at tumour testing with ION Torrent. In addition, according with filtering criteria used in a previous study, which focused on germline variants29, we considered only homopolymeric indels with an absolute VAF above 15% and in any case higher than the maximum value of the control population at each homopolymeric region. Lastly, regions with a total read count of less than 100 were excluded from the analysis.

Targeted Sanger sequencing was performed on tumour DNA to confirm the occurrence of outlier homopolymeric indels selected by using the defined thresholds.

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