biostudies-literatureVite CHGerman Research FoundationNICHD NIH HHSRace for AdamNCRR NIH HHSNiemann-Pick Type C DiseaseNIHNational Niemann-Pick Disease FoundationDana's Angels Research TrustNIDDK NIH HHSAra Parseghian Medical Research FoundationNINDS NIH HHSNIH HHSPHS HHS276ra26https://www.ebi.ac.uk/biostudies/studies/S-EPMC4415615biostudies-literatureUnknown7(276)Niemann-Pick type C1 (NPC) disease is a lysosomal storage disease caused by mutations in the NPC1 gene, leading to an increase in unesterified cholesterol and several sphingolipids, and resulting in hepatic disease and progressive neurological disease. We show that subcutaneous administration of the pharmaceutical excipient 2-hydroxypropyl-β-cyclodextrin (HPβCD) to cats with NPC disease ameliorated hepatic disease, but doses sufficient to reduce neurological disease resulted in pulmonary toxicity. However, direct administration of HPβCD into the cisterna magna of presymptomatic cats with NPC disease prevented the onset of cerebellar dysfunction for greater than a year and resulted in a reduction in Purkinje cell loss and near-normal concentrations of cholesterol and sphingolipids. MoreoverScience translational medicineIntracisternal cyclodextrin prevents cerebellar dysfunction and Purkinje cell death in feline Niemann-Pick type C1 disease.PMC4415615P40-02512R01-NS073661DFG-STE 1069/2-1R01 NS081985P40 RR002512P40 OD010939P30 DK020579R01 NS073661R01 NS053677R01-HD045561P30 HD071593U54 HD086984Swain GPBagel JHKao MLWalkley SUO'Donnell PStein VMDe Meulder MWard SStellar SVite CHLi SCrooks AOry DSDavidson CRuane TVanier MTSikora TUProciuk MMauldin EfalseIntracisternal cyclodextrin prevents cerebellar dysfunction and Purkinje cell death in feline Niemann-Pick type C1 disease.Niemann-Pick type C1 (NPC) disease is a lysosomal storage disease caused by mutations in the NPC1 gene, leading to an increase in unesterified cholesterol and several sphingolipids, and resulting in hepatic disease and progressive neurological disease. We show that subcutaneous administration of the pharmaceutical excipient 2-hydroxypropyl-β-cyclodextrin (HPβCD) to cats with NPC disease ameliorated hepatic disease, but doses sufficient to reduce neurological disease resulted in pulmonary toxicity. However, direct administration of HPβCD into the cisterna magna of presymptomatic cats with NPC disease prevented the onset of cerebellar dysfunction for greater than a year and resulted in a reduction in Purkinje cell loss and near-normal concentrations of cholesterol and sphingolipids. Moreover2015-01-01T00:00:00Z2015 Feb2025-04-19T00:49:36.266Z2019-03-27T01:50:57ZS-EPMC44156152571709910.1126/scitranslmed.3010101