Abstract
Purpose
Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal disorder caused
by pathogenic variants in NPC1. Disease progression is monitored using the NPC Neurological Severity Scale, but
there are currently no established validated or qualified biomarkers. Neurofilament
light chain (NfL) is being investigated as a biomarker in multiple neurodegenerative
diseases.
Methods
Cross-sectional and longitudinal cerebrospinal fluid (CSF) samples were obtained from
116 individuals with NPC1. NfL levels were measured using a solid-phase sandwich enzyme-linked
immunosorbent assay and compared with age-appropriate non-NPC1 comparison samples.
Results
Median levels of NfL were elevated at baseline (1152 [680-1840] pg/mL) in NPC1 compared
with controls (167 [82-372] pg/mL; P < .001). Elevated NfL levels were associated with more severe disease as assessed
by both the 17-domain and 5-domain NPC Neurological Severity Score. Associations were
also observed with ambulation, fine motor, speech, and swallowing scores. Although
treatment with the investigational drug 2-hydroxypropyl-β-cyclodextrin (adrabetadex)
did not decrease CSF NfL levels, miglustat therapy over time was associated with a
decrease (odds ratio = 0.77, 95% CI = 0.62-0.96).
Conclusion
CSF NfL levels are increased in individuals with NPC1, associated with clinical disease
severity, and decreased with miglustat therapy. These data suggest that NfL is a biomarker
that may have utility in future therapeutic trials.
Keywords
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Article info
Publication history
Published online: December 02, 2022
Accepted:
November 28,
2022
Received in revised form:
November 28,
2022
Received:
July 8,
2022
Identification
Copyright
Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics.
