Codon-Optimized Gene Therapy for Niemann-Pick Disease Type C

Niemann Pick Disease Type C (NPC) is a rare and fatal, autosomal recessive, neurodegenerative disease that can present in infants, children, or adults. Most patients with NPC have mutations in NPC1, a gene implicated in intracellular cholesterol trafficking, which results in intracellular accumulation of unesterified cholesterol in late edosomal/lysosomal structures and of glycosphingolipids, especially in neuronal tissue. No curative therapy exists at present.

Adding to their previous work and patent portfolio of NPC gene constructs, NHGRI investigators have generated improved and codon-optimized gene vectors. These new adeno-associated viral (AAV) vectors have been shown to clear or significantly remove accumulated cellular cholesterol in human mutant NPC1 cell models. In addition to codon-optimization, the vectors can include various tags (e.g., a protein transduction domain peptide, which allows for trans-cellular correction of cells that have not been infected with therapy vector), specialized promoter to increase expression, strong translation initiation site, and/or multiple stop signals.