2-Hydroxypropyl-β-cyclodextrins and the Blood-Brain Barrier: Considerations for Niemann-Pick Disease Type C1.

ABSTRACT: The rare, chronic, autosomal-recessive lysosomal storage disease Niemann-Pick disease type C1 (NPC1) is characterized by progressively debilitating and ultimately fatal neurological manifestations. There is an urgent need for disease-modifying therapies that address NPC1 neurological pathophysiology, and passage through the blood-brain barrier represents an important consideration for novel NPC1 drugs. Animal investigations of 2-hydroxypropyl-β-cyclodextrins (HPβCD) in NPC1 in mice demonstrated that HPβCD does not cross the blood-brain barrier in significant amounts but suggested a potential for these complex oligosaccharides to moderately impact CNS manifestations when administered subcutaneously or intraperitoneally at very high doses; however, safety concerns regarding pulmonary toxicit

SUBMITTER: Calias P 

PROVIDER: S-EPMC5824462 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature