Neurofilament light chain in cerebrospinal fluid as a novel biomarker in evaluating both clinical severity and therapeutic response in Niemann-Pick disease type C1.

Autor:	Agrawal N; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD., Farhat NY; Division of Translational Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD., Sinaii N; Biostatistics and Clinical Epidemiology Service, Clinical Center, National Institues of Health, Bethesda, MD., Do AD; Division of Translational Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD., Xiao C; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD., Berry-Kravis E; Department of Neurological Sciences, Department of Pediatrics, Department of Biochemistry, Rush University Medical Center, Chicago, IL., Bianconi S; Division of Translational Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD; Southern California Permanente Medical Group, San Diego, CA., Masvekar R; Neuroimmunological Diseases Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Bielekova B; Neuroimmunological Diseases Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Solomon B; Rehabilitaiton Medicine Department, Mark O. Hatfield Clinical Research Center, National Institutes of Health, Bethesda, MD., Porter FD; Division of Translational Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. Electronic address: fdporter@mail.nih.gov.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2023 Mar; Vol. 25 (3), pp. 100349. Date of Electronic Publication: 2022 Dec 05.
DOI:	10.1016/j.gim.2022.11.017
Abstrakt:	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. Competing Interests: Conflict of Interest The authors declare no conflicts of interest. (Published by Elsevier Inc.)
Databáze:	MEDLINE
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