Gene therapy restores immune function in children with rare immunodeficiency – National Institutes of Health
By daniellenierenberg
News Release
Tuesday, May 11, 2021
An investigational gene therapy can safely restore the immune systems of infants and children who have a rare, life-threatening inherited immunodeficiency disorder, according to research supported in part by the National Institutes of Health. The researchers found that 48 of 50 children who received the gene therapy retained their replenished immune system function two to three years later and did not require additional treatments for their condition, known as severe combined immunodeficiency due to adenosine deaminase deficiency, or ADA-SCID. The findings were published today inthe New England Journal of Medicine.
ADA-SCID, which is estimated to occur in approximately 1 in 200,000 to 1,000,000 newborns worldwide, is caused by mutations in theADAgene that impair the activity of the adenosine deaminase enzyme needed for healthy immune system function. This impairment leaves children with the condition highly susceptible to severe infections. If untreated, the disease is fatal, usually within the first two years of life.
These findings suggest that this experimental gene therapy could serve as a potential treatment option for infants and older children with ADA-SCID, said Anthony S. Fauci, M.D., director of NIHs National Institute of Allergy and Infectious Diseases (NIAID). Importantly, gene therapy is a one-time procedure that offers patients the hope of developing a completely functional immune system and the chance to live a full, healthy life.
People with ADA-SCID can be treated with enzyme replacement therapy, but this treatment does not fully reconstitute immune function and must be taken for life, usually once or twice weekly. Transplants of blood-forming stem cells, ideally from a genetically matched sibling donor, can provide a more lasting solution. However, most people lack such a donor. Additionally, stem cell transplants carry risks such asgraft-versus-host disease and side effects from chemotherapy medications given to help the donor stem cells establish themselves in the patients bone marrow.
The new research evaluated an experimental lentiviral gene therapy designed to be safer and more effective than previously tested gene-therapy strategies for ADA-SCID. This gene therapy involves inserting a normal copy of theADAgene into the patients own blood-forming stem cells. First, stem cells are collected from the patients bone marrow or peripheral blood. Next, a harmless virus is used as a vector, or carrier, to deliver the normalADAgene to these cells in the laboratory. The genetically corrected stem cells then are infused back into the patient, who has received a low dose of the chemotherapy medication busulfan to help the cells establish themselves in the bone marrow and begin producing new immune cells.
The experimental gene therapy, developed by researchers from the University of California, Los Angeles (UCLA) and Great Ormond Street Hospital (GOSH) in London, uses a modified lentivirus to deliver the ADA gene to cells. Previous gene-therapy approaches for ADA-SCID have relied on a different type of virus called a gamma retrovirus. Some people who have received gamma retroviral gene therapies have later developed leukemia, which scientists suspect is due to the vector causing activation of genes that control cell growth.The lentiviral vector is designed to avoid this outcome and to enhance the effectiveness of gene delivery into cells.
The results come from three separate Phase 1/2 clinical trials, two conducted in the United States and one in the United Kingdom. The U.S. trials, led by principal investigator Donald Kohn, M.D., of UCLA, enrolled 30 participants with ADA-SCID ranging in age from 4 months to 4 years at UCLA Mattel Childrens Hospital and the NIH Clinical Center in Bethesda, Maryland. The U.K. study, conducted at GOSH and led by principal investigator Claire Booth, M.B.B.S., Ph.D., enrolled 20 participants ranging in age from 4 months to 16 years. Most participants acquired and retained robust immune function following gene therapy 96.7% after two years in the U.S. studies and 95% after three years in the U.K. study and were able to stop enzyme replacement therapy and other medications. Of the two participants for whom gene therapy did not restore lasting immune function, one restarted enzyme replacement therapy and later received a successful stem cell transplant from a donor, and the other restarted enzyme replacement therapy. The lentiviral gene therapy appeared safe overall, although all participants experienced some side effects. Most of these were mild or moderate and attributable to the chemotherapy that the participants received.
Researchers observed similar outcomes in all three trials, although there were some differences between the studies. Stem cells were collected from bone marrow in the U.S. trials and from peripheral blood in the U.K. trial. In one of the U.S. trials, 10 children were treated with genetically corrected stem cells that had been frozen and later thawed. The two other trials used fresh stem cell preparations. In the future, the freezing procedure known as cryopreservation may allow stem cells to be more easily transported and processed at a manufacturing facility far from the patients home and shipped back to a local hospital, reducing the need for patients to travel long distances to specialized medical centers to receive gene therapy. A trial of the cryopreserved treatment is now underway at the Zayed Centre for Research into Rare Diseases in Children in London, in partnership with GOSH.
For more information about the trials described in the New England Journal of Medicine paper, visit ClinicalTrials.gov under identifiers NCT01852071, NCT02999984 and NCT01380990. The investigational lentiviral gene therapy, which is licensed to Orchard Therapeutics, has not been approved for use by any regulatory authority.
The research was funded in part by three NIH Institutes: NIAID; the National Heart, Lung and Blood Institute; and the National Human Genome Research Institute. Additional funding was provided by the California Institute for Regenerative Medicine, the Medical Research Council, the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children National Health Service Foundation Trust and University College London, and Orchard Therapeutics.
NIAID conducts and supports research at NIH, throughout the United States, and worldwide to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.
About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.
NIHTurning Discovery Into Health
DB Kohn, C Boothet al. Autologousex vivolentiviral gene therapy for adenosine deaminase deficiency.New England Journal of MedicineDOI: 10.1056/NEJMoa2027675 (2021).
###
Read the rest here:
Gene therapy restores immune function in children with rare immunodeficiency - National Institutes of Health
- 5 year old boy from Iraq undergoes world's first of its kind bone marrow transplantation in India - The Times of India - March 31st, 2025
- Superior outcomes of haploidentical hematopoietic cell transplantation over chemotherapy in AML patients 55 years or older - Nature.com - March 31st, 2025
- Blood and Marrow Transplantation and Cellular Therapy Center - NYU Langone Health - March 22nd, 2025
- Bone Marrow Transplantation Market Poised to Achieve USD 14,336 Billion by 2031 - Persistence Market Research - openPR - March 22nd, 2025
- BioRestorative Therapies to Report 2024 Financial Results and Host Conference Call on March 27, 2025 - The Manila Times - March 22nd, 2025
- Man Cured Of Sickle Cell Disease In New York Thanks To New Gene Therapy - Forbes - March 22nd, 2025
- Boost in cancer treatment: PGI working on lab for stem cell, gene therapies - The Times of India - March 22nd, 2025
- Clonal dynamics and somatic evolution of haematopoiesis in mouse - Nature.com - March 11th, 2025
- Mitochondria-enriched hematopoietic stem cells exhibit elevated self-renewal capabilities, thriving within the context of aged bone marrow -... - March 11th, 2025
- TET2 deficiency increases the competitive advantage of hematopoietic stem and progenitor cells through upregulation of thrombopoietin receptor... - March 11th, 2025
- Garuda Therapeutics Closes $50 Million Series A-1 Financing to Advance Off-the-Shelf Blood Stem Cell Therapies - GlobeNewswire - March 11th, 2025
- Abu Dhabi Stem Cells Center and Yas Clinic first in UAE to receive AABB accreditation for haematopoietic progenitor cell collection - Abu Dhabi Media... - March 11th, 2025
- Discovery of lung-based blood stem cells may transform transplant therapies - Medical Xpress - March 1st, 2025
- VUMC part of new study validating curative therapy for sickle cell disease - VUMC Reporter - March 1st, 2025
- What Is the Role of MRD Testing Before HSCT in MDS/MPN? - DocWire News - March 1st, 2025
- Melphalan-based conditioning with post-transplant cyclophosphamide for peripheral blood stem cell transplantation: donor effect - Nature.com - March 1st, 2025
- Mesenchymal Stem Cells Market Projected to Reach USD 11.26 Billion by 2034, Growing at a CAGR of 12.9% - openPR - March 1st, 2025
- See snazzy slugs in all their luminous glory Februarys best science images - Nature.com - March 1st, 2025
- On the origin of neutrophils - Nature.com - March 1st, 2025
- Four-year-old donates stem cells to save her baby sister from blood cancer in Odisha - The Hindu - February 20th, 2025
- Effect of pre-transplant cytoreductive therapy on the outcomes of patients with MDS or secondary AML evolving from MDS undergoing allo-HSCT: a... - February 20th, 2025
- A heart disease trigger that lurks inside bone marrow - Harvard Health - February 20th, 2025
- 4-year-old donates stem cells to save sister as SCB performs first-of-a-kind bone marrow transplant in Odisha - OTV News - February 20th, 2025
- KU Cancer Center recognized for transplant that saved 1-year-olds life - WDAF FOX4 Kansas City - February 20th, 2025
- Orca-T With RIC Is Safe in Advanced Hematologic Malignancies - OncLive - February 20th, 2025
- SCB conducts Odisha's first bone marrow transplant on two-year-old - The New Indian Express - February 20th, 2025
- Bahrain's pioneering use of sickle cell disease treatment hailed by medical experts - The National - February 20th, 2025
- Cancer survivor is the first monumental bone marrow transplant patient in Baton Rouge in 8 years - NOLA.com - February 11th, 2025
- Autologous Cell Therapy Market to Hit Valuation of US$ 44.55 Billion By 2033 | Astute Analytica - GlobeNewswire - February 11th, 2025
- Nanoparticle that cuts middlemen could improve stem cell therapy - Futurity: Research News - January 31st, 2025
- GATA2 mutated allele specific expression is associated with a hyporesponsive state of HSC in GATA2 deficiency syndrome - Nature.com - January 31st, 2025
- Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy - Science - January 31st, 2025
- How the bone marrow microbiome responds to immunotherapy - Chemical & Engineering News - January 31st, 2025
- My Experience With Stem Cell Therapy: Snake Oil or Silver Bullet? - GearJunkie - January 31st, 2025
- Hematopoietic Stem Cell Transplantation - StatPearls - NCBI ... - January 22nd, 2025
- Doctors retrieve stem cells from 20-month-old to treat thalassaemic sister - The Times of India - January 22nd, 2025
- YolTech Therapeutics to Initiate a Clinical Trial for YOLT-204, a First-in-Class Bone Marrow-Targeted In Vivo Gene Editing Therapy for -Thalassemia -... - January 22nd, 2025
- School of Medicine professor receives grant to study improved cancer treatments - Mercer University - January 14th, 2025
- 1st stem cell therapy, new HIV drug approved - ecns - January 5th, 2025
- Suppression of thrombospondin-1mediated inflammaging prolongs hematopoietic health span - Science - January 5th, 2025
- A pilot raced through the airport to surprise an old friend: the woman who saved his life - CNN - December 27th, 2024
- Types of Stem Cell and Bone Marrow Transplants - December 27th, 2024
- Explained: What is mesenchymal stem cell therapy? - Drug Discovery News - December 18th, 2024
- Stem Cell Transplants Offer New Hope for Saving the Worlds Corals - Technology Networks - December 18th, 2024
- Scientists Present Research on Novel Cancer Therapies at ASH - City of Hope - December 18th, 2024
- Navigating CAR-T cell therapy long-term complications - Nature.com - December 18th, 2024
- High-dose chemotherapy followed by autologous stem cell transplant ineffective for patients with mantle cell lymphoma - News-Medical.Net - December 18th, 2024
- Stem Cell Therapy Market Is Expected To Reach Revenue Of - GlobeNewswire - December 18th, 2024
- The Importance of Cellular Therapy in the Clinical Case of a Young Man With a Challenging Precursor B-cell Lymphoblastic Leukemia - Cureus - December 18th, 2024
- A search for the perfect match, Apex six year old in need of donor - CBS17.com - December 18th, 2024
- New insights into survival of breast cancer cells in the bone marrow - News-Medical.Net - December 9th, 2024
- Cellular trafficking and fate mapping of cells within the nervous system after in utero hematopoietic cell transplantation - Nature.com - December 9th, 2024
- Saving lives, one stem cell at a time - Texas A&M The Battalion - December 9th, 2024
- Turn Biotechnologies Announces Landmark Study to Assess Effectiveness of ERA Therapy in Restoring Bone Marrow - PR Newswire UK - December 9th, 2024
- Orca Bio Presents Three-Year Survival Data with Orca-T in Patients with Hematological Malignancies at the 66th ASH Annual Meeting - Yahoo Finance - December 9th, 2024
- You are the match. How UNC student honored her late grandfather with life-saving effort - Raleigh News & Observer - November 29th, 2024
- scRNA-seq revealed transcriptional signatures of human umbilical cord primitive stem cells and their germ lineage origin regulated by imprinted genes... - November 29th, 2024
- Atlanta pilot with an aggressive cancer finds lifesaving help from a stranger and a simple test - The Atlanta Journal Constitution - November 29th, 2024
- Researchers have brought the promise of stem cell therapies closer to reality - The Week - November 29th, 2024
- Bone Marrow Donors Can Be Hard to Find. One Company Is Turning to ... - November 15th, 2024
- Hematopoietic Stem Cells and Their Niche in Bone Marrow - November 15th, 2024
- Bone Marrow Transplant Program - Overview - Mayo Clinic - November 15th, 2024
- Bone Marrow Donors Can Be Hard to Find. One Company Is Turning to Cadavers - WIRED - November 15th, 2024
- More stem cells for sickle cell gene therapy readied with motixafortide - Sickle Cell Disease News - November 15th, 2024
- Skull bone marrow expands throughout life and remains healthy during aging, researchers discover - Medical Xpress - November 15th, 2024
- Adult skull bone marrow is an expanding and resilient haematopoietic reservoir - Nature.com - November 15th, 2024
- Evaluation of standard fludarabine dosing and corresponding exposures in infants and young children undergoing hematopoietic cell transplantation -... - November 15th, 2024
- Stem cells grown in space show super powers but theres a catch - Study Finds - November 15th, 2024
- Getting a Stem Cell or Bone Marrow Transplant - October 21st, 2024
- Acquisition of durable insulin-producing cells from human adipose tissue-derived mesenchymal stem cells as a foundation for cell- based therapy of... - October 21st, 2024
- 1.5 Lakh Indians Register To Save Lives: Join the Mission To Fight Blood Cancer - The Better India - October 21st, 2024
- How Stem Cell and Bone Marrow Transplants Are Used to Treat Cancer - October 13th, 2024
- Stem Cell (Bone Marrow) Transplants - MD Anderson Cancer Center - October 13th, 2024
- Donating Bone Marrow and Stem Cells: The Process and What To Expect - October 13th, 2024
- What to expect as a stem cell or bone marrow donor - October 13th, 2024
- Structural organization of the bone marrow and its role in ... - October 13th, 2024
- Stem cell donor from down the road saved my life after global search - BBC.com - September 23rd, 2024
- Awaiting the call: family hopes to find blood stem cell donor - Claremont Courier - September 23rd, 2024
- Michigan woman one of first in world to successfully receive bone marrow from deceased donor - WDIV ClickOnDetroit - September 23rd, 2024
- Next-generation stem cell transplant: Revolutionizing a lifesaving cancer therapy - The Business Journals - September 23rd, 2024
