Niemann-Pick Disease Type C (NPC) is a rare progressive genetic disorder characterized by dysfunction of NPC1 protein leading to inability of the body to transport cholesterol and other fatty substances inside of cells. Abnormal cholesterol accumulation in the major organs lead to organ dysfunction, organ failure, and death.

Medical needs

Miglustat is the first and only specific drug approved for NPC in Europe, Canada and Japan. While Miglustat has shown to alleviate disease symptoms while attenuating neurodegeneration, some studies suggest its limited efficacy in NPC. In the US, the FDA declined its approval, requiring for more data. Hydroxypropyl-beta-cyclodextrin (HPβCD) has been used compassionately to treat patients with NPC and is undergoing clinical trials. HPβCD has shown to facilitate cholesterol transport inside of cells and its efflux. HPβCD is given to patients through either intrathecal or intravenous administration. Unfortunately, permanent hearing loss can occur following HPβCD therapy, with either route resulting in the preferential loss of cochlear outer hair cells (OHCs).

Mechanism of action

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Cyclodextrin has shown to reduce both cholesterol and sphingolipid storage within cells and to prolong survival in NPC animal models. RN-005 has shown cholesterol efflux efficacy superior to HPβCD.