Neurofilament light chain in cerebrospinal fluid as a novel biomarker in evaluating both clinical severity and therapeutic response in Niemann-Pick disease type C1.
Cerebral spinal fluid biomarker
NPC1
Neurofilament light
Niemann-Pick Disease, type C1
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
08
07
2022
revised:
28
11
2022
accepted:
28
11
2022
pmc-release:
01
03
2024
pubmed:
6
12
2022
medline:
9
3
2023
entrez:
5
12
2022
Statut:
ppublish
Résumé
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. 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. 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). 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.
Identifiants
pubmed: 36470574
pii: S1098-3600(22)01037-1
doi: 10.1016/j.gim.2022.11.017
pmc: PMC9992339
mid: NIHMS1872696
pii:
doi:
Substances chimiques
miglustat
ADN3S497AZ
2-Hydroxypropyl-beta-cyclodextrin
1I96OHX6EK
Biomarkers
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100349Subventions
Organisme : Intramural NIH HHS
ID : ZIA HD008988
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA HD008989
Pays : United States
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Conflict of Interest The authors declare no conflicts of interest.
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