A study from NIH has used the Olink® Explore high-throughput proteomics platform to identify biomarkers that could prove useful in the development of future therapies for Niemann-Pick disease, type C1 (NPC1), an ultrarare recessive condition with mostly paediatric onset and ultimately lethal neurological consequences, for which there are no approved therapies.
The Olink Explore platform was used to compare the levels of ~1500 proteins in cerebrospinal fluid (CSF) from patients with and without NPC1, identifying multiple proteins with significantly different levels in the NPC1 CSF proteome. These included proteins previously reported to be elevated in NPC1 (NEFL, MAPT, CHIT1, CALB1) as well as several novel potential biomarkers in this context (PARK7, CALB2, CHI3L1/YKL-40, MIF, CCL18 and ENO2). The differentially expressed proteins that had not been reported previously were orthogonally verified using ELISAs, providing supporting evidence for their associations with the disease. In further analyses aimed at exploring links to disease phenotypes, a strong negative correlation was observed between CCL18 and age of neurological onset for childhood/adolescent cases, while a strong positive correlation was seen for CCL18 and the Annual Severity Increment Score (ASIS) that is used clinically to monitor disease progression. These data identified and validated multiple proteins in CSF from individuals with NPC1 that are candidates for more extensive investigations and which may prove to be useful as supportive data in future therapeutic trials.