Poly(GR) and poly(GA) in cerebrospinal fluid as potential biomarkers for C9ORF72-ALS/FTD.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 05 2022
19 05 2022
Historique:
received:
14
11
2021
accepted:
29
04
2022
entrez:
19
5
2022
pubmed:
20
5
2022
medline:
24
5
2022
Statut:
epublish
Résumé
GGGGCC repeat expansion in C9ORF72, which can be translated in both sense and antisense directions into five dipeptide repeat (DPR) proteins, including poly(GP), poly(GR), and poly(GA), is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we developed sensitive assays that can detect poly(GA) and poly(GR) in the cerebrospinal fluid (CSF) of patients with C9ORF72 mutations. CSF poly(GA) and poly(GR) levels did not correlate with age at disease onset, disease duration, or rate of decline of ALS Functional Rating Scale, and the average levels of these DPR proteins were similar in symptomatic and pre-symptomatic patients with C9ORF72 mutations. However, in a patient with C9ORF72-ALS who was treated with antisense oligonucleotide (ASO) targeting the aberrant C9ORF72 transcript, CSF poly(GA) and poly(GR) levels decreased approximately 50% within 6 weeks, indicating they may serve as sensitive fluid-based biomarkers in studies directed against the production of GGGGCC repeat RNAs or DPR proteins.
Identifiants
pubmed: 35589711
doi: 10.1038/s41467-022-30387-4
pii: 10.1038/s41467-022-30387-4
pmc: PMC9119980
doi:
Substances chimiques
Biomarkers
0
C9orf72 Protein
0
C9orf72 protein, human
0
Dipeptides
0
Proteins
0
poly(glycyl-alanyl)
0
Banques de données
ClinicalTrials.gov
['NCT01925196']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2799Subventions
Organisme : NINDS NIH HHS
ID : R01 NS078398
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS111990
Pays : United States
Organisme : NINDS NIH HHS
ID : P01 NS099114
Pays : United States
Organisme : NINDS NIH HHS
ID : P01 NS084974
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS113943
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS101986
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS097273
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS097542
Pays : United States
Organisme : NINDS NIH HHS
ID : R37 NS057553
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072931
Pays : United States
Informations de copyright
© 2022. The Author(s).
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