NIH to Advance Gene Therapy Trial for Rare Metabolic Disorder After Biotech Pullout
核心洞察
NIH and NHGRI collaborate to advance a gene therapy trial for methylmalonic acidemia (搜索) (MMA (搜索)) after Selecta Biosciences (搜索) halted the project due to financial reasons.
The trial, expected to begin in fall 2025, will use AAV8 (搜索) to deliver a healthy copy of the _MMUT_ (搜索) gene, offering hope for MMA (搜索) patients with limited treatment options.
NCATS is committing $2.2 million over five years and leveraging its expertise in gene therapy to support the trial, which could streamline future rare disease trials at NIH.
Following Selecta Biosciences (搜索)' decision to discontinue a clinical trial for a promising gene therapy targeting a rare metabolic disease, methylmalonic acidemia (搜索) (MMA (搜索)), the National Institutes of Health (NIH) and the National Human Genome Research Institute (NHGRI) have stepped in to collaborate and move the research forward. The clinical trial, anticipated to commence in the fall of 2025, offers renewed hope for individuals affected by this rare condition and could establish a framework for similar trials at NIH.
The project, initiated in 2016 between Selecta Biosciences (搜索) and NHGRI researcher Charles Venditti, M.D., Ph.D., aimed to develop a gene therapy for MMA (搜索), specifically targeting a faulty methylmalonyl-CoA mutase (MMUT) gene. MMA is a rare, often life-threatening genetic disorder affecting the liver, preventing the breakdown of certain proteins and fats, leading to a buildup of harmful substances in the body. This buildup can cause various symptoms, including lethargy, dehydration, kidney disease, brain fog, and intellectual disabilities.
Preclinical Success and Subsequent Halt
Venditti's team and Selecta scientists conducted preclinical studies demonstrating the potential benefit of gene therapy using adeno-associated virus 8 (AAV8 (搜索)) and an immune system-modulating agent in a mouse model. These studies led to a successful Investigational New Drug (IND) application with the FDA. However, weeks before the planned clinical trial at the NIH Clinical Center, Selecta Biosciences (搜索) halted the project due to financial constraints.
NIH's Intervention and Trial Details
To maintain momentum, NCATS is committing approximately $2.2 million over five years through its Cures Acceleration Network. Selecta's donation of regulatory documentation and two batches of the therapy further facilitated the new trial. The Phase 1/2 trial will assess the safety and potential efficacy of delivering a functional copy of the MMUT gene to a small cohort of patients with MMA (搜索).
Collaborative Effort and Future Implications
NCATS will provide project coordination and technical expertise in clinical product storage and stability testing, as well as assist with regulatory document preparation. Other NIH institutes, including the National Institute of Neurological Disorders and Stroke (NINDS) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), will also contribute to the trial. According to NCATS Director Joni Rutter, Ph.D., this collaboration underscores their commitment to providing new hope for people with rare diseases and could accelerate future rare disease trials at NIH.
The MMA (搜索)-101 trial has the potential to inform other gene therapy initiatives, such as the Platform Vector Gene Therapy (PaVe-GT) project and the Bespoke Gene Therapy Consortium (BGTC), potentially streamlining the development process and reducing barriers to commercialization. The ultimate goal, according to Venditti, is to democratize gene therapy by lowering costs and increasing accessibility.