Niemann-Pick disease, type C1 (NPC1), is a rare, fatal, neurodegenerative lysosomal disorder caused by pathological variants in Proximal Extension Assays (PEA) were used to determine relative protein Show more
Niemann-Pick disease, type C1 (NPC1), is a rare, fatal, neurodegenerative lysosomal disorder caused by pathological variants in Proximal Extension Assays (PEA) were used to determine relative protein expression levels from 68 serum samples from NPC1 individuals and 20 age-appropriate control serum samples. Statistical models identified NPC1 disease-specific effects after adjusting for covariates. Selected proteins were orthogonally validated by ELISA and correlated with assessments of both disease severity (Age of Neurological Onset (ANO) and Annual Severity Increment Score (ASIS)) and disease burden (NPC Neurological Severity Score (NSS). Quantifiable data was obtained on 2888 proteins, revealing 186 increased (adjusted log The statistical analysis pipeline developed in this study is flexible and scalable and supports application to high-dimensional proteomic datasets. This study identified and validated serum proteins with altered expression in individuals with NPC1, responded to miglustat therapy, and correlated with disease severity or burden. These proteins may have clinical utility as biomarkers and provide insights into cellular mechanisms contributing to NPC1 disease pathology. NCT00344331 (Registration on 2006-06-23). Show less