Media Advisory

Thursday, October 12, 2023

Novel conditioning agent shows promise in animal models of sickle cell disease.

Researchers at the National Institutes of Health have created a novel gene therapy procedure that could preserve fertility in people with sickle cell disease and other genetic blood conditions. Infertility is a high-risk and long-term side effect associated with current bone marrow transplantation and gene therapy approaches to treat sickle cell disease. It is a common reason people of reproductive age give for not pursuing these therapies.

The study, which appears in Nature Communications, describes the successful testing in animals of an antibody-drug conjugate, or conditioning agent, that exclusively targets blood-forming stem cells in the bone marrow. Conditioning agents are used in gene therapy to remove diseased stem cells and allow healthy stem cells to form. This new agent, called CD117-ADC, does not appear to damage other organs during the conditioning process. It is less toxic than the conventional agent now used for gene therapy in humans, called busulfan, which may cause ovarian failure in women and may stop sperm production in men, resulting in infertility.

Researchers found that CD117-ADC allowed robust engraftment of gene-modified cells to increase fetal hemoglobin, a type of oxygen-carrying blood protein present at birth. When used in adults with sickle cell disease, fetal hemoglobin can reduce complications associated with the disease, and reactivating and increasing its production is a promising goal for gene therapy. Unlike busulfan, the new conditioning agent also was shown to preserve fertility in females and males.

The paper, Fertility-preserving myeloablative conditioning using single dose CD117 antibody-drug conjugate in a rhesus gene therapy model, published Oct. 12 in the Nature Communications.

John F. Tisdale, M.D., chief of the Cellular and Molecular Therapeutics Branch of the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, and Naoya Uchida, M.D., Ph.D., a staff scientist in the branch, are available to discuss this study.

To request an interview with Drs. Tisdale and Uchida, please email nhlbi_news@nhlbi.nih.gov

About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit http://www.nhlbi.nih.gov.

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.

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