Researchers at the National Institutes of Health (NIH) have developed an innovative gene therapy approach that has the potential to safeguard fertility in individuals with sickle cell disease and other genetic blood disorders. The often high-risk and long-term side effect of infertility has been associated with current bone marrow transplantation and gene therapy methods used to treat sickle cell disease.
This obstacle discourages many individuals of reproductive age from pursuing these life-changing therapies. The study details the successful testing of an antibody-drug conjugate, or conditioning agent, in animal models. This agent, known as CD117-ADC, selectively targets blood-forming stem cells in the bone marrow. Conditioning agents play a crucial role in gene therapy by eliminating diseased stem cells, making way for healthy ones to take their place.
What sets CD117-ADC apart is its apparent lack of detrimental effects on other organs during the conditioning process. It is also notably less toxic than the conventional agent used in human gene therapy, called busulfan. Busulfan has been known to cause ovarian failure in women and disrupt sperm production in men, often leading to infertility.Â
The researchers discovered that CD117-ADC facilitated robust engraftment of gene-modified cells, resulting in an increase in fetal hemoglobin, a type of oxygen-carrying blood protein present at birth. When utilized in adults with sickle cell disease, elevating fetal hemoglobin levels can reduce complications associated with the disease.
Reactivating and enhancing fetal haemoglobin production is a promising objective for gene therapy in these individuals. Importantly, unlike busulfan, the new conditioning agent demonstrated the ability to preserve fertility in both females and males.Â
Sickle cell disease is a hereditary blood disorder characterized by abnormally shaped red blood cells. These deformed cells can lead to a range of health issues, including pain, organ damage, and increased risk of infection. Current treatment options often include bone marrow transplants or gene therapy to correct the genetic mutation responsible for the disease.
However, these treatments can come with significant side effects, including the risk of infertility, which has been a substantial deterrent for many patients, particularly those of reproductive age. The novel approach developed by the NIH researchers represents a potential game-changer in the field of gene therapy for sickle cell disease and other genetic blood conditions.
CD117-ADC has shown promise in animal testing by effectively conditioning the bone marrow to support the engraftment of gene-modified cells. This is significant because gene therapy aims to replace the defective blood-forming stem cells with healthy ones, potentially curing the underlying genetic disorder.Â
Furthermore, the study findings reveal that the conditioning agent CD117-ADC has a notably lower risk of damaging other organs, unlike busulfan, which has been associated with infertility issues in both women and men. Preserving fertility in individuals undergoing gene therapy for sickle cell disease is a crucial advancement, as it addresses one of the primary concerns that have discouraged people from seeking these life-improving treatments.Â
NIH researchers have introduced a promising gene therapy strategy with the development of CD117-ADC, a conditioning agent that offers potential benefits in treating sickle cell disease and other genetic blood disorders. By enabling successful engraftment of gene-modified cells and simultaneously preserving fertility in both men and women, this novel approach could transform the lives of individuals living with these conditions and encourage more patients to consider gene therapy as a viable option for treatment.Â
Reference Â
National Institute of Health (NIH), “NIH researchers work to preserve fertility for people undergoing gene therapy” https://www.nih.gov/news-events/news-releases/nih-researchers-work-preserve-fertility-people-undergoing-gene-therapyÂ
