Niemann-Pick Disease, type C1 (NPC1) is a neurodegenerative disorder due to a defect in intracellular lipid and cholesterol transport. As part of a Bench-to-Bedside initiative, we initiated a clinical protocol focused on identifying and characterizing biomarkers that could be used in a subsequent therapeutic trial. Funding to support a research nurse was provided by both the Ara Parseghian Medical Research Foundation and Danas Angels Research Trust. This protocol was initiated in August 2006, and to date we have enrolled seventyfive NPC patients. This is the largest cohorts of actively followed patients in this country. While most of the patients are children, the patients range in age from infants to adults. This protocol involves neurological, hearing, ophthalmological, psychiatric and medical evaluations. Blood, urine, and cerebral spinal fluid are being collected for biomarker analysis. Evaluations include magnetic resonance imaging combined with spectroscopy and auditory brainstem responses. We plan to continue to enroll new patients and follow this group over time. This initial observational study was instrumental in laying the foundation for a therapeutic trial of N-acetyl cystein that was initiated in September 2009. This trial was a placebo-controlled, cross-over trial that enrolled 35 NPC patients. This trial was completed in August 2010. In early 2013 we initiate a phase I trial of hydroxypropyl-beta-cyclodextran administered directly to the central nervous system in collaboration with the Therapuetics and Rare Disease Section of NCATS and multiple extramural investigators. Work is ongoing in aniticpation of organizing a multicenter clinical efficacy trial.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Zip Code
Tseng, Wei-Chia; Loeb, Hannah E; Pei, Wuhong et al. (2018) Modeling Niemann-Pick disease type C1 in zebrafish: a robust platform for in vivo screening of candidate therapeutic compounds. Dis Model Mech 11:
Cougnoux, Antony; Drummond, Rebecca A; Collar, Amanda L et al. (2018) Microglia activation in Niemann-Pick disease, type C1 is amendable to therapeutic intervention. Hum Mol Genet 27:2076-2089
Cougnoux, Antony; Movassaghi, Miyad; Picache, Jaqueline A et al. (2018) Gastrointestinal Tract Pathology in a BALB/c Niemann-Pick Disease Type C1 Null Mouse Model. Dig Dis Sci 63:870-880
Dai, Sheng; Dulcey, Andrés E; Hu, Xin et al. (2017) Methyl-?-cyclodextrin restores impaired autophagy flux in Niemann-Pick C1-deficient cells through activation of AMPK. Autophagy :1-17
Ory, Daniel S; Ottinger, Elizabeth A; Farhat, Nicole Yanjanin et al. (2017) Intrathecal 2-hydroxypropyl-?-cyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: a non-randomised, open-label, phase 1-2 trial. Lancet 390:1758-1768
Newton, Jason; Hait, Nitai C; Maceyka, Michael et al. (2017) FTY720/fingolimod increases NPC1 and NPC2 expression and reduces cholesterol and sphingolipid accumulation in Niemann-Pick type C mutant fibroblasts. FASEB J 31:1719-1730
Chandler, Randy J; Williams, Ian M; Gibson, Alana L et al. (2017) Systemic AAV9 gene therapy improves the lifespan of mice with Niemann-Pick disease, type C1. Hum Mol Genet 26:52-64
Höglinger, Doris; Nadler, André; Haberkant, Per et al. (2017) Trifunctional lipid probes for comprehensive studies of single lipid species in living cells. Proc Natl Acad Sci U S A 114:1566-1571
Salman, Alexander; Cougnoux, Antony; Farhat, Nicole et al. (2017) Association of NPC1 variant p.P237S with a pathogenic splice variant in two Niemann-Pick disease type C1 patients. Am J Med Genet A 173:1038-1040
Wassif, Christopher A; Cross, Joanna L; Iben, James et al. (2016) High incidence of unrecognized visceral/neurological late-onset Niemann-Pick disease, type C1, predicted by analysis of massively parallel sequencing data sets. Genet Med 18:41-8

Showing the most recent 10 out of 51 publications