A combinatorial therapeutic approach to treating cholesterol storage disorders that may drastically reduce the dosage of HPβCD required for treatment of NPC. Proof-of-concept has been demonstrated in NPC mutant cells. The new therapeutic approach is based on the unexpected discovery that a lipid based molecule, itself previously thought of as an excipient, can clear cholesterol from late endosomes and lysosomes in Npc1-/- cells. Combinatorial formulations, co-administration, and other means of achieving the synergistic reduction of stored cholesterol should avoid toxicity issues with current HPβCD dosage regimens. The technology may also provide additional opportunities for treating a variety of cholesterol storage disorders.
Features & Benefits
Background of Invention
Niemann Pick Type C (NPC) is an inherited cholesterol storage disorder that affects approximately 1:120,000 children globally and results in hepatomegaly, progressive neurodegeneration, and finally death. 2-Hydroxy-propyl-β-cyclodextrin (HPβCD), once considered a non-active excipient, has been identified as capable of cholesterol efflux and redistribution in mammalian cells. The FDA has granted orphan drug status to HPβCD; however, toxicity with the dosage required remains a problem.
Patent pending (U.S. provisional patent application)