Category Archives: Genetic Medicine

- Intracochlear delivery of a dual AAVAnc80 vector encoding human otoferlin results in full-length protein expression in inner hair cells of non-human primates and in durable protein expression sufficient for sustained restoration of auditory function in Otof knockout mice

- Multiple analyses demonstrate in vitro transduction with dual AK-OTOF vector results in full-length otoferlin expression, with no detection of truncated proteins

- Long-term, local expression of anti-VEGF protein is robust and well tolerated following intracochlear administration of AK-antiVEGF in non-human primates

- Akouos continues to progress towards planned IND submissions for AK-OTOF in the first half of 2022 and for AK-antiVEGF in 2022

BOSTON, May 11, 2021 (GLOBE NEWSWIRE) -- Akouos, Inc. (NASDAQ: AKUS), a precision genetic medicine company dedicated to developing potential gene therapies for individuals living with disabling hearing loss worldwide, today presented nonclinical data supporting the future clinical development of both AK-OTOF, a gene therapy intended for the treatment of otoferlin gene (OTOF)-mediated hearing loss, and AK-antiVEGF, a gene therapy intended for the treatment of vestibular schwannoma, in three digital presentation sessions at the virtual American Society of Gene and Cell Therapy (ASGCT) 24th Annual Meeting.

We are excited to share new data that highlight the potential of genetic medicines for inner ear conditions with the broader gene therapy community, said Manny Simons, Ph.D., M.B.A., co-founder, president, and chief executive officer of Akouos. Inner ear conditions represent one of the largest areas of unmet need in medicine today, and one of the challenges in this area is the ability to efficiently address the broad range of conditions that collectively affect hundreds of millions of individuals worldwide. The nonclinical data presented today for the AK-OTOF and AK-antiVEGF programs demonstrate how we are leveraging our genetic medicines platform and multiple AAV-mediated modalities, including gene transfer and therapeutic protein expression, to begin to address that challenge.

Nonclinical data presented at ASGCT for AK-OTOF continue to support the potential to restore physiologic hearing and provide long-lasting benefit to individuals with OTOF-mediated hearing loss. In Otof knockout mice, AK-OTOF administration results in durable expression of human otoferlin protein sufficient for sustained restoration of auditory function. In addition, data presented indicate that expression of exogenous secreted protein at or above reported biologically active levels, driven by a ubiquitous promoter, is well tolerated in non-human primates following administration of AK-antiVEGF. These IND-enabling nonclinical studies are promising and support future clinical development. Our team continues to work towards submission of INDs for AK-OTOF and AK-antiVEGF expected in 2022, said Greg Robinson, Ph.D., chief scientific officer of Akouos.

In Vitro and In Vivo Analyses of Dual Vector Otoferlin Expression to Support the Clinical Development of AK-OTOF (AAVAnc80-hOTOF Vector)

Presenting Author: Eva Andres-Mateos

Abstract Number: 355

Otoferlin plays a critical role in exocytosis of synaptic vesicles at the inner hair cell synapse, and mutations inOTOF, the gene encoding otoferlin, are associated with autosomal recessive sensorineural hearing loss. AK-OTOF is designed to deliver normal OTOF by utilizing a dual vector approach,which encodes the 5 and the 3 components of OTOF. Multiple analyses demonstrate in vitro transduction with dual AK-OTOF vector results in full-length human otoferlin (RNA and protein), with no detection of truncated proteins from either AK-OTOF or its component vectors (5hOTOF and 3hOTOF). A one-to-one ratio of the AK-OTOF component vectors appears to be optimal for efficient reconstitution of full-length human otoferlin. In cynomolgus macaques, full-length human otoferlin protein expression is detected in inner hair cells of non-human primate (NHP) cochleae by both immunohistochemistry and immunodetection one month following intracochlear administration of AAVAnc80-FLAG.hOTOF.

The digital presentation is located at https://akouos.com/gene-therapy-resources/.

Durable Recovery of Auditory Function Following Intracochlear Delivery of AK-OTOF (AAVAnc80-hOTOF Vector) in a Translationally Relevant Mouse Model of Otoferlin Gene (OTOF)-Mediated Hearing Loss

Presenting Author: Ann Hickox

Abstract Number: 569

Otoferlin gene (OTOF)-mediated hearing loss is caused by mutations in the OTOF gene and is typically characterized by a congenital, Severe to Profound sensorineural hearing loss. The physiologic deficiency resulting from OTOF mutations is localized; specifically, synaptic transmission between the inner hair cell and the auditory nerve is affected, as measured by an absent or abnormal auditory brain stem response (ABR). Gene therapy for OTOF-mediated hearing loss is expected to confer the greatest benefit when cochlear integrity is preserved, as represented by present otoacoustic emissions (OAEs). Individuals with OTOF-mediated hearing loss typically experience a decline in cochlear integrity within the first decade of life, indicated by initially present, then absent, OAEs. In an Otof knockout mouse model that recapitulates the human phenotype, administration of AK-OTOF, an adeno-associated viral gene therapy vector encoding human otoferlin under the control of a ubiquitous promoter, results in durable restoration of auditory function, as measured by ABRs, and may preserve OAEs.

The digital presentation is located at https://akouos.com/gene-therapy-resources/.

Demonstration of Tolerability of a Novel Delivery Approach and Secreted Protein Expression Following Intracochlear Delivery of AK-antiVEGF (AAVAnc80-antiVEGF Vector) in Non-Human Primates

Presenting Author: John Connelly

Abstract Number: 358

Data published from previous clinical trialsshow that systemic VEGF inhibitor therapy can reduce vestibular schwannoma (VS) tumor volume and improve hearing in some participants with mutations in the NF2 gene. However, toxicity limits the potential of this systemic delivery approach from being a viable treatment option for vestibular schwannoma. The exposure and tolerability of local expression of anti-VEGF protein following bilateral, intracochlear administration of AK-antiVEGF was evaluated through analyses of protein levels, as well as physiologic and histologic evaluations, in NHPs. Long-term, local expression of anti-VEGF protein, driven by a ubiquitous promoter, is robust and well tolerated in NHPs following intracochlear administration of AK-antiVEGF. Computational modelling supports the potential for diffusion of anti-VEGF protein at or above reported biologically active levels to the site of the VS tumor.

The digital presentation is located at https://akouos.com/gene-therapy-resources/.

About Akouos

Akouos is a precision genetic medicine company dedicated to developing gene therapies with the potential to restore, improve, and preserve high-acuity physiologic hearing for individuals living with disabling hearing loss worldwide. Leveraging its precision genetic medicine platform that incorporates a proprietary adeno-associated viral (AAV) vector library and a novel delivery approach, Akouos is focused on developing precision therapies for forms of sensorineural hearing loss. Headquartered in Boston, Akouos was founded in 2016 by leaders in the fields of neurotology, genetics, inner ear drug delivery, and AAV gene therapy.

Cautionary Note Regarding Forward-Looking Statements

Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the initiation, plans, and timing of our future clinical trials and our research and development programs, the timing of our IND submissions for AK-OTOF and AK-antiVEGF, our expectations regarding our manufacturing capabilities and timelines, and the period over which we believe that our existing cash, cash equivalents and marketable securities will be sufficient to fund our operating expenses. The words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, should, target, will, would, and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: our limited operating history; uncertainties inherent in the development of product candidates, including the initiation and completion of nonclinical studies and clinical trials; whether results from nonclinical studies will be predictive of results or success of clinical trials; the timing of and our ability to submit applications for, and obtain and maintain regulatory approvals for, our product candidates; our expectations regarding our regulatory strategy; our ability to fund our operating expenses and capital expenditure requirements with our cash, cash equivalents, and marketable securities; the potential advantages of our product candidates; the rate and degree of market acceptance and clinical utility of our product candidates; our estimates regarding the potential addressable patient population for our product candidates; our commercialization, marketing, and manufacturing capabilities and strategy; our ability to obtain and maintain intellectual property protection for our product candidates; our ability to identify additional products, product candidates, or technologies with significant commercial potential that are consistent with our commercial objectives; the impact of government laws and regulations; risks related to competitive programs; the potential that our internal manufacturing capabilities and/or external manufacturing supply may experience delays; the impact of the COVID-19 pandemic on our business, results of operations, and financial condition; our ability to maintain and establish collaborations or obtain additional funding; and other factors discussed in the Risk Factors included in the Companys Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission, and in other filings that the Company makes with the Securities and Exchange Commission in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and the Company expressly disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.

Contacts

Media:Katie Engleman, 1ABkatie@1abmedia.com

Investors:Courtney Turiano, Stern Investor RelationsCourtney.Turiano@sternir.com

Read more here:
Akouos Presents Nonclinical Data Supporting Future Clinical Development of AK-OTOF and AK-antiVEGF at the American Society of Gene and Cell Therapy...

New leadership includes Andrea Paul as general counsel and corporate secretary, and Janice Olson as senior vice president, strategy and portfolio management, bringing extensive experience in gene therapy and rare disease

LEXINGTON, Mass., May 10, 2021 /PRNewswire/ -- LogicBio Therapeutics, Inc. (Nasdaq:LOGC), a clinical-stage genetic medicine company pioneering gene delivery and gene editing platforms to address rare and serious diseases from infancy through adulthood, today announced the appointment of Andrea Paul as general counsel and corporate secretary and Janice Olson as senior vice president of strategy and portfolio management. Ms. Paul and Ms. Olson are both seasoned industry experts with extensive experience in the pharmaceutical and biotechnology industries including in the gene therapy and rare disease sectors.

"It is an exciting time at LogicBio with ongoing efforts to expand the reach of our GeneRide and sAAVy platforms validated by our recent collaboration deals with Daiichi Sankyo and CANbridge Pharmaceuticals. Adding key talent across the team is essential to our success and I look forward to working with Andrea and Janice, whose broad industry experience will be instrumental as we further strengthen our leadership position in the development of next-generation genetic medicines," said Frederic Chereau, president and chief executive officer of LogicBio Therapeutics.

Andrea Paul, General Counsel and Corporate Secretary

Ms. Paul joins LogicBio Therapeutics as general counsel and corporate secretary, effective May 17, 2021, bringing several years of experience in the pharmaceutical and biotechnology industries. She is currently at Akebia Therapeutics, Inc., where she has held roles of increasing responsibility, most recently serving as vice president, legal. While at Akebia, Ms. Paul was a key strategic legal partner in the company's merger with Keryx Biopharmaceuticals, Inc. as well as in the company's financing and business development transactions. Prior to Akebia, she served as senior corporate counsel at Momenta Pharmaceuticals, Inc. Before that, she was an associate at Mintz Levin and Sullivan & Cromwell LLP. She received her JD from Harvard Law School, where she served as the managing editor of the Harvard Law Review, and her BA from Columbia University (Columbia College). Ms. Paul currently serves as the co-chair of the Securities Law Committee of the Boston Bar Association.

"I am excited to be joining the executive team at LogicBio. The Company is deeply committed to patients, and I look forward to helping the team deliver the benefits of genetic medicine to the fight against early onset childhood diseases," said Ms. Paul.

Janice Olson, Senior Vice President, Strategy and Portfolio Management

Ms. Olson joins LogicBio Therapeutics as senior vice president, strategy and portfolio management, effective June 7, 2021. Previously, she spent more than 25 years at Genzyme (now Sanofi Genzyme) holding multiple roles, most recently serving as head of global medical affairs operations, starting in January 2016. Before that, Ms. Olson served as vice president of portfolio and program management for the Genzyme R&D center. During her time at Genzyme, she developed extensive experience managing and coordinating multi-disciplinary teams for numerous R&D projects from discovery through launch. She has also served as program lead for multiple gene therapy programs developed worldwide. Ms. Olson received her MBA and BS in biology from Northeastern University.

"I am thrilled to become part of LogicBio's amazing journey at such a transformative step of its development, and I am looking forward to helping the team and the Company's new strategic partners advance programs forward for patients with significant unmet needs," said Ms. Olson.

The Company also announced the resignation of Kyle Chiang, PhD, who will be stepping down as chief operating officer, effective May 28, 2021, to pursue an opportunity at a venture capital firm focusing on early-stage sustainability and life sciences focused ventures. Dr. Chiang will consult with the Company over the next several months to ensure a smooth transition.

"I would like to thank Kyle for his commitment over the early years of the Company and wish him the best as he enters a new field. With the additions announced today, we are further strengthening our leadership team, and I am confident we are well positioned to continue to expand our platforms and pipeline in the years ahead," added Mr. Chereau.

About LogicBio Therapeutics, Inc.

LogicBio Therapeutics is a clinical-stage genetic medicine company pioneering gene delivery and gene editing platforms to address rare and serious diseases from infancy through adulthood. The company's proprietary GeneRide platform is a new approach to precise gene insertion that harnesses a cell's natural DNA repair process leading to durable therapeutic protein expression levels. LogicBio's cutting-edge sAAVy capsid development platform is designed to support development of treatments in a broad range of indications and tissues. The company is based in Lexington, MA. For more information, visit https://www.logicbio.com/.

Media Contacts:

Adam DaleyBerry & Company Public RelationsW: 212-253-8881C: 614-580-2048adaley@berrypr.com

Jenna UrbanBerry & Company Public RelationsW: 212-253-8881C: 203-218-9180jurban@berrypr.com

Investor Contacts:

Matt LaneGilmartin Group617-901-7698matt@gilmartinir.com

View original content:http://www.prnewswire.com/news-releases/logicbio-therapeutics-strengthens-management-team-with-key-appointments-301287264.html

SOURCE LogicBio Therapeutics, Inc.

Company Codes: NASDAQ-NMS:LOGC

Read this article:
LogicBio Therapeutics Strengthens Management Team with Key Appointments - BioSpace

Visit the News Hub

Study to look for genetic pathways that lead to formation of plaques, tangles

A $10.7 million, five-year grant will support a comprehensive study in which whole genome sequencing will be used to address critical gaps in knowledge about Alzheimer's disease. The project is led by researchers at Washington University School of Medicine in St. Louis and the University of Pittsburgh Graduate School of Public Health.

Despite decades of research and investment, the genetic underpinnings of Alzheimers disease are still largely unknown, stymieing efforts at drug development and early diagnosis. To change that, a new grant will support the first comprehensive study to use whole genome sequencing to address critical gaps in knowledge about the disease. The $10.7 million, five-year project is led by researchers at Washington University School of Medicine in St. Louis and the University of Pittsburgh Graduate School of Public Health.

Funded by the National Institute on Aging of the National Institutes of Health (NIH), the research team plans to identify the genetic variants, genes and pathways that lead to formation of plaques and tangles, two specific signs of disease called biomarkers that begin appearing in the brains of people with Alzheimers 15 to 25 years before they show symptoms.

Cruchaga

Genetic studies of measurable traits such as plaques and tangles provide advantages over other classic case-control studies, because these traits appear earlier and are more closely related to the biology behind the disease, said Carlos Cruchaga, PhD, a co-principal investigator of the study and the Reuben Morriss III Professor of Neurology at Washington University School of Medicine. In addition, studying these traits is more likely to lead to the identification of druggable targets along the genetic pathways that lead to disease. This genetic information can help us better predict disease risk at the individual patient level.

Cruchaga, also a professor of psychiatry, is working with co-principal investigator Ilyas Kamboh, PhD, a professor of human genetics and epidemiology at Pitt Public Health. Together, they plan to study as many as 5,000 participants at high risk for Alzheimers. The researchers will gather biomarker data to identify genetic variants that appear decades before clinical symptoms of the disease.

All of the clinical trials to find a drug to stop Alzheimers disease have failed because theyve focused on patients who already have developed the disease, so they already had high levels of plaques and tangles, said Kamboh. Once you have the plaques and tangles, it seems to be an irreversible process, so were focused on the preclinical stage of the disease.

According to the World Health Organization, Alzheimers disease is the most common form of dementia, with about 50 million cases worldwide and 6 million new cases each year. It is one of the major causes of disability and dependency among older people.

The plaques and tangles in the brain associated with Alzheimers can be thought of like cholesterol in the arteries of the heart and its association with heart disease, Kamboh explained. Cholesterol can quietly accumulate over years along the walls of the coronary arteries without causing symptoms until it causes a heart attack and does irreversible damage to the heart. Some genes predispose people to accumulate more cholesterol, and understanding that can allow people to take medication and make lifestyle changes that reduce the risk of heart disease. It also can prompt pharmaceutical companies to develop drugs that target the genetic pathways that lead to the formation of cholesterol deposits.

The new project will look for the genetic underpinnings of the plaques and tangles known to define Alzheimers disease and that formed due to abnormal accumulation of amyloid beta and tau proteins, respectively. Both can be detected early in the brains of living people through neuroimaging and the testing of cerebrospinal fluid.

In the past, we could detect these plaques and tangles only after death, through a brain autopsy, Kamboh said. Now we can identify them while people are living.

But those imaging and fluid-collection techniques are expensive and can be invasive.

New methods are now being developed to detect the presence of abnormal amyloid beta and tau proteins in less expensive blood tests, Cruchaga said. We hope that by learning more about the genes associated with the plaques and tangles, we might uncover underlying pathways that lead to Alzheimers disease and discover potential drug targets.

This study is supported by the National Institute on Aging of the National Institutes of Health (NIH). Grant number R01 AG064877.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, consistently ranking among the top medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

Follow this link:
WashU, Pitt awarded $10.7 million for Alzheimer's disease research Washington University School of Medicine in St. Louis - Washington University...

A gene calledGAS2plays a key role in normal hearing, and its absence causes severe hearing loss, according to a study led by researchers in Penns Perelman School of Medicine.

The researchers, whose findings arepublished online inDevelopmental Cell, discovered that the protein encoded byGAS2is crucial for maintaining the structural stiffness of support cells in the inner ear that normally help amplify incoming sound waves. They showed that inner ear support cells lacking functionalGAS2lose their amplifier abilities, causing severe hearing impairment in mice. The researchers also identified people who haveGAS2mutations and severe hearing loss.

Anatomists 150 years ago took pains to draw these support cells with the details of their unique internal structures, but its only now, with this discovery aboutGAS2, that we understand the importance of those structures for normal hearing, says study senior authorDouglas J. Epstein, professor of genetics at Penn Medicine.

Two to three of every 1,000 children in the United States are born with hearing loss in one or both ears. About half of these cases are genetic. Although hearing aids and cochlear implants often can help, these devices seldom restore hearing to normal.

One of the main focuses of the Epstein laboratory at Penn Medicine is the study of genes that control the development and function of the inner eargenes that are often implicated in congenital hearing loss. The inner ear contains a complex, snail-shaped structure, the cochlea, that amplifies the vibrations from sound waves, transduces them into nerve signals, and sends those signals toward the auditory cortex of the brain.

Read more at Penn Medicine News.

Visit link:
Discovery of a new genetic cause of hearing loss illuminates how inner ear works | Penn Today - Penn Today

BETHESDA, Md., May 13, 2021 /PRNewswire/ --The National Coordinating Center for the Regional Genetics Network (NCC) is excited to announce the second annual Public Health Genetics Week from May 24-28, 2021. The goal of Public Health Genetics Week is to increase awareness and to celebrate the field of public health genetics.

Each day of Public Health Genetics Week will have a different theme:

Individuals and organizations are encouraged to participate in the week by using the hashtags #PHGW and #PublicHealthGenetics across their social media platforms.

The following events will also occur throughout the week:

Ken Burns Presents The Gene: An Intimate HistoryVirtual Screening

In collaboration with WETA Washington, D.C., virtual daily screenings of Ken Burns Presents The Gene: An Intimate History ("THE GENE") will be held to celebrate Public Health Genetics Week. The landmark four-hour documentary seriesweaves together science, history, and personal stories to present a historical biography of the human genome, while also exploring groundbreaking breakthroughs for diagnosis and treatment of genetic diseases, and the complex web of moral, ethical and scientific questions raised by developments in genetics.

Listed below is the virtual screening schedule. More information, including registration information, can be found at https://phgw.org/thegene.

For more information about the film, visit https://pbs.org/thegene.

Social Media Events

Other Activities

OnPHGW.org, everyone can find more information about the daily themes, social media events, and social media tools (such as daily social media images, GIFs, social media banners, and more).

For questions or comments about Public Health Genetics Week, please contact [emailprotected]and be sure to follow NCC (@nccrcg) onFacebook,Instagram,LinkedIn,TikTok, andTwitterfor the latest updates on the week.

About the National Coordinating Center for the Regional Genetics Networks (NCC)

Funded since 2004 by the Health Resources and Services Administration/Maternal and Child Health Bureau (MCHB) to the American College of Medical Genetics and Genomics (ACMG), NCC's mission is to improve access to genetic services for underserved populations. In collaboration with the seven Regional Genetics Network (RGNs) and the National Genetics Education and Family Support Center (NGEFSC), NCC achieves this mission by working in the following focus areas: genetics and genomics education; genetics policy education; telemedicine; and data collection and evaluation. Learn more about the efforts of the NCC athttps://nccrcg.org.

NCC Funding Acknowledgement

This project is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under Cooperative Agreement #UH9MC30770-01-00 from June 2020 to May 2024 for $800,000 per award year.

This information or content and conclusions are those of the author and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS or the U.S. government.

About Ken Burns Presents The Gene: An Intimate History

Ken Burns Presents The Gene: An Intimate Historyis a production of Florentine Films and WETA Washington, D.C., in association with Ark Media. Executive Producer and Senior Creative Consultant: Ken Burns. Written by Geoffrey C. Ward; and Barak Goodman & David Blistein. Based on the book "The Gene: An Intimate History" by Dr. Siddhartha Mukherjee. Narrator: David Costabile. Senior Producer: Barak Goodman. Directors: Chris Durrance and Jack Youngelson. Executive Producers: Dr. Siddhartha Mukherjee, Dalton Delan, Tom Chiodo, John F. Wilson and Anne Harrington. Production funding has been provided by Genentech, 23andMe, Cancer Treatment Centers of America, Alfred P. Sloan Foundation, Gray Foundation, American Society of Clinical Oncology (ASCO) & Conquer Cancer Foundation, Judy and Peter Blum Kovler Foundation, Craig and Susan McCaw Foundation, and the Corporation for Public Broadcasting. The Outreach and Education Partner is National Institutes of Health, National Human Genome Research Institute. Outreach support is provided by Foundation Medicine.

About WETA Washington, D.C.

WETA Washington, D.C., is a leading producer of new content for public television in the United States. WETA productions and co-productions include PBS NewsHour; Washington Week; documentaries by filmmaker Ken Burns, including Ken Burns Presents The Gene: An Intimate History, Cancer: The Emperor of all Maladies, Hemingway and the forthcoming MuhammadAli;and series and specials by scholar Henry Louis Gates, Jr., including Finding Your Roots, Reconstruction: America After the Civil War and The Black Church: This Is Our Story, This Is Our Song. WETA's multi-year campaign Well Beings addresses the critical health needs of Americans. More information on WETA and its programs and services is available at weta.org. On social media, visit facebook.com/wetatvfmon Facebook and follow @WETAtvfmon Twitter.

Related Images

image1.png

SOURCE National Coordinating Center for the Regional Genetics Networks (NCC)

Go here to see the original:
National Coordinating Center for the Regional Genetics Network (NCC) Announces the Second Annual Public Health Genetics Week, May 24-28, 2021 -...

Gene therapy has shown promise in recent years for treating a range of diseases, including sickle-cell anemia, hemophilia, various forms of inherited blindness, mesothelioma, and Duchenne muscular dystrophy. A new success story may soon be added to this list, with the publication yesterday of the outcomes of a clinical trial that used gene therapy to cure a rare immune system disorder in infants.

The study, described in the New England Journal of Medicine, was carried out by researchers from UCLA and Great Ormond Street Hospital in London over the course of five years, beginning in 2012.

Adenosine deaminase (ADA) is an enzyme found in a type of white blood cell called lymphocytes, which are primarily active in the brain, GI tract, and thymus gland. Lymphocytes make antibodies and attack infected cells, so theyre pretty crucial to the immune system.

ADAs job is to convert a molecule thats harmful to lymphocytes into a non-harmful version of itself. If ADA cant work its magic, that molecule starts to build up in lymphocytes, becoming toxic and ultimately killing the cellsand leaving the immune system virtually defenseless, highly vulnerable to invaders like viruses and bacteria.

Mutations in the ADA gene mean the body doesnt make enough of the enzyme to successfully do its job. This deficiency of ADA leads to a condition called severe combined immunodeficiency (SCID). Those suffering from SCID can not only get sick very easily, but conditions that would be neutralized by a normal immune system quickly become deadly for them.

SCID was more commonly known as bubble boy disease after David Vetter, a boy born in Texas in 1971, spent 12 of his 13 years of life enclosed in a plastic bubble to protect him from germs.

About 20 different genetic mutations can cause SCID; ADA-SCID refers to immunodeficiency caused by lack of the ADA enzyme: severe combined immunodeficiency due to adenosine deaminase deficiencya bit of a mouthful. The worst part of ADA-SCID is that it occurs in babies; most are diagnosed with the condition before theyre even six months old, and without treatment they typically dont live past age two.

ADA is rare, estimated to occur in about 1 in 200,000 to 1,000,000 newborns worldwide; both the mothers and the fathers ADA gene must have mutations for the child to end up with this condition.

The first step in the gene therapy treatment was to collect hematopoietic stem cells, which are those that manufacture blood cells, from the patients. The researchers then inserted an intact copy of the ADA gene into the stem cells using an RNA virus called a lentivirus (the most well-known lentivirus is HIV).

The altered cells were re-injected into the patients, where they started producing ADA normally, yielding healthy immune cells.

Out of 50 total patients30 in the US and 20 in the UKwith ADA-SCID, 48 appear to have been rid of their condition thanks to the gene therapy, with no complications reported. The two patients who didnt have success with the therapy went back to traditional treatment methods, and didnt experience any adverse effects as a result of having tried the therapy.

If, or hopefully when, gene therapy becomes the go-to treatment for ADA-SCID, it will be a welcome reprieve from traditional options, which are neither pleasant nor cheap: patients need weekly injections of ADA until a bone marrow transplant can be done, and absent a donor, they must consistently receive injections, take antibiotics, and undergo antibody infusions for life.

If approved in the future, this treatment could be standard for ADA-SCID, and potentially many other genetic conditions, removing the need to find a matched donor for a bone marrow transplant and the toxic side effects often associated with that treatment, said Dr. Claire Booth, co-author of the study and a consultant in pediatric immunology and gene therapy at Londons Great Ormond Street Hospital.

Theres no mention of the cost of the therapy, nor whether this could be a prohibitive factor to making it a viable option. Nonetheless, the study is encouraging not just for its potential to revolutionize treatment of ADA-SCID, but as a harbinger for the promise of gene therapy for a multitude of genetic conditions.

People ask us, is it a cure? Who knows long term, but at least up to three years, these children are doing well, said Dr. Stephen Gottschalk, who was not involved in this study but performed a similar gene therapy on kids with SCID at St. Jude Childrens Research Hospital in Memphis. The immune function seems stable over time so I think it looks very, very encouraging.

Image Credit: liyuanalison from Pixabay

Read more:
How One Round of Gene Therapy Fixed 48 Kids' Immune Systems - Singularity Hub