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 fifty-six 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. Work is now in progress to implement a clinical trial focused on characterizing protein biomarkers in the cerebral spinal fluid of NPC1 patients. In collaboration with the Therapuetics and Rare Disease Section of NCATS and multiple extramural investigators, we are initiating a therapuetic trial of cyclodextrin in NPC1.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2012
Total Cost
$338,195
Indirect Cost
City
State
Country
Zip Code
Mazzacuva, Francesca; Mills, Philippa; Mills, Kevin et al. (2016) Identification of novel bile acids as biomarkers for the early diagnosis of Niemann-Pick C disease. FEBS Lett 590:1651-62
Bradbury, Allison; Bagel, Jessica; Sampson, Maureen et al. (2016) Cerebrospinal Fluid Calbindin D Concentration as a Biomarker of Cerebellar Disease Progression in Niemann-Pick Type C1 Disease. J Pharmacol Exp Ther 358:254-61
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
Cologna, Stephanie M; Shieh, Christine; Toth, Cynthia L et al. (2016) Altered cerebrospinal fluid proteins in Smith-Lemli-Opitz syndrome patients. Am J Med Genet A 170:2060-2068
Nicoli, Elena-Raluca; Al Eisa, Nada; Cluzeau, Celine V M et al. (2016) Defective Cytochrome P450-Catalysed Drug Metabolism in Niemann-Pick Type C Disease. PLoS One 11:e0152007
Thurm, Audrey; Tierney, Elaine; Farmer, Cristan et al. (2016) Development, behavior, and biomarker characterization of Smith-Lemli-Opitz syndrome: an update. J Neurodev Disord 8:12
Thurm, Audrey; Farmer, Cristan; Farhat, Nicole Yanjanin et al. (2016) Cohort study of neurocognitive functioning and adaptive behaviour in children and adolescents with Niemann-Pick Disease type C1. Dev Med Child Neurol 58:262-9
Cougnoux, A; Cluzeau, C; Mitra, S et al. (2016) Necroptosis in Niemann-Pick disease, type C1: a potential therapeutic target. Cell Death Dis 7:e2147
Jiang, Xuntian; Sidhu, Rohini; Mydock-McGrane, Laurel et al. (2016) Development of a bile acid-based newborn screen for Niemann-Pick disease type C. Sci Transl Med 8:337ra63
Darnell, Andrew J; Austin, Howard; Bluemke, David A et al. (2016) A Clinical Service to Support the Return of Secondary Genomic Findings in Human Research. Am J Hum Genet 98:435-41

Showing the most recent 10 out of 42 publications