Direct Brain Administration Increases Efficacy of Niemann-Pick Disease Treatment

A new data review concludes that 2-hydroxypropyl-β-cyclodextrin (HPβCD) does not cross the blood-brain barrier (BBB) in therapeutically relevant amounts to address the neurological manifestations of Niemann-Pick Disease Type C1 (NPC1). These manifestations vary with age of onset and include delay in developmental motor milestones, gait problems, falls, clumsiness, vertical supranuclear gaze palsy, cerebellar ataxia, dysarthria, dysphagia and progressive dementia. Based upon physicochemical properties, findings in animal models, early clinical studies, and patient case reports, the evidence to date suggests that HPβCD does not cross the BBB in therapeutically relevant amounts in the NPC1 setting. Direct administration to the central nervous system (CNS) would be expected to provide the greatest NPC1 neurological efficacy and is supported by a phase 1/2a clinical study. The review is published in the Current Pharmaceutical Design.

NPC1 is an autosomal-recessive, rare lysosomal storage characterized by progressively debilitating and ultimately fatal neurological manifestations. Clinical trials of different HPβCD agents are currently underway and the route of administration is an important point of consideration for the anticipated results of these trials with regard to safety, tolerability and efficacy in the NPC1 population.

Cyclodextrins are complex mixtures of different chemical species and different cyclodextrin products are therefore not the same as one another. When administering drugs directly to the CNS, it is important that the agent being administered is highly purified and well characterized to avoid introducing any contaminants and/or unknown agents that could adversely affect neurological development and/or function. Currently, VTS-270 is the only specific and well-characterized mixture of HPβCD, with a tightly controlled molar substitution specification and a defined molecular "fingerprint" of the different chemical species present in the mixture based on Kleptose® HPB (Roquette Pharma, France).



Source-Eurekalert