Randy Chandler (NHGRI)
William Pavan (NHGRI)
Investigators at the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH) are seeking collaborators to further develop gene therapy to treat Niemann-Pick Disease Type C (NPC). NPC is a rare, autosomal recessive, neurodegenerative disease. Approximately 95% of patients with NPC have mutations in NPC1, a gene implicated in intracellular cholesterol trafficking. Mutations of NPC1 cause intracellular accumulation of unesterified cholesterol in late endosomal/lysosomal structures and marked accumulation of glycosphingolipids, especially in neuronal tissue. Thus, NPC patients generally present with hepatosplenomegaly (enlargement of liver and spleen) and neurological degeneration.
NHGRI investigators have generated adeno-associated viral (AAV) constructs that are able to correct cellular defects of certain cholesterol storage disease or disorders, such as NPC, in vivo.
- Potential for successful gene therapy for patients with NPC.
- Can lead to similar approaches for treating other cholesterol storage disorders.
- Optimized components of the vectors (e.g., specific promoters).
- Shown to work in animal (murine) models.