NFL is a marker of treatment response in children with SMA treated with nusinersen.
Biomarkers
Cerebrospinal fluid
Neurofilament
SMA
Tau
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Sep 2019
Sep 2019
Historique:
received:
07
01
2019
accepted:
17
05
2019
revised:
11
04
2019
pubmed:
28
5
2019
medline:
29
1
2020
entrez:
25
5
2019
Statut:
ppublish
Résumé
Recently, the anti-sense oligonucleotide drug nusinersen was approved for spinal muscular atrophy (SMA) and our aim was to find a response marker for this treatment. Twelve children with SMA type 1 and two copies of the SMN2 gene were included in a consecutive single-center study. The children were sampled for CSF at baseline and every time nusinersen was given intrathecally. The neuronal biomarkers NFL and tau and the glial biomarker GFAP were measured. Motor function was assessed using CHOP INTEND. Eleven similarly aged children, who were investigated to rule out neurological or infectious disease, were used as controls. Baseline levels of NFL (4598 ± 981 vs 148 ± 39, P = 0.001), tau (939 ± 159 vs 404 ± 86, P = 0.02), and GFAP (236 ± 44 vs 108 ± 26, P = 0.02) were significantly higher in SMA children than controls. Motor function improved by nusinersen treatment in median 13 points corresponding to 5.4 points per month of treatment (P = 0.001). NFL levels typically normalized ( < 380 pg/ml) between the fourth and fifth doses [- 879.5 pg/mL/dose, 95% CI (- 1243.4, - 415.6), P = 0.0001], tau levels decreased [- 112.6 pg/mL/dose, 95% CI (- 206-7, - 18.6), P = 0.01], and minor decreases in GFAP were observed [- 16.9 pg/mL/dose, 95% CI (- 22.8, - 11.2), P = 0.02] by nusinersen treatment. Improvement in motor function correlated with reduced concentrations of NFL (rho = - 0.64, P = 0.03) and tau (rho = - 0.85, P = 0.0008) but not GFAP. Nusinersen normalized the axonal damage marker NFL and correlated with motor improvement in children with SMA. NFL may, therefore, be a novel biomarker to monitor treatment response early in the disease course.
Sections du résumé
BACKGROUND
BACKGROUND
Recently, the anti-sense oligonucleotide drug nusinersen was approved for spinal muscular atrophy (SMA) and our aim was to find a response marker for this treatment.
METHODS
METHODS
Twelve children with SMA type 1 and two copies of the SMN2 gene were included in a consecutive single-center study. The children were sampled for CSF at baseline and every time nusinersen was given intrathecally. The neuronal biomarkers NFL and tau and the glial biomarker GFAP were measured. Motor function was assessed using CHOP INTEND. Eleven similarly aged children, who were investigated to rule out neurological or infectious disease, were used as controls.
RESULTS
RESULTS
Baseline levels of NFL (4598 ± 981 vs 148 ± 39, P = 0.001), tau (939 ± 159 vs 404 ± 86, P = 0.02), and GFAP (236 ± 44 vs 108 ± 26, P = 0.02) were significantly higher in SMA children than controls. Motor function improved by nusinersen treatment in median 13 points corresponding to 5.4 points per month of treatment (P = 0.001). NFL levels typically normalized ( < 380 pg/ml) between the fourth and fifth doses [- 879.5 pg/mL/dose, 95% CI (- 1243.4, - 415.6), P = 0.0001], tau levels decreased [- 112.6 pg/mL/dose, 95% CI (- 206-7, - 18.6), P = 0.01], and minor decreases in GFAP were observed [- 16.9 pg/mL/dose, 95% CI (- 22.8, - 11.2), P = 0.02] by nusinersen treatment. Improvement in motor function correlated with reduced concentrations of NFL (rho = - 0.64, P = 0.03) and tau (rho = - 0.85, P = 0.0008) but not GFAP.
CONCLUSIONS
CONCLUSIONS
Nusinersen normalized the axonal damage marker NFL and correlated with motor improvement in children with SMA. NFL may, therefore, be a novel biomarker to monitor treatment response early in the disease course.
Identifiants
pubmed: 31123861
doi: 10.1007/s00415-019-09389-8
pii: 10.1007/s00415-019-09389-8
pmc: PMC6687695
doi:
Substances chimiques
Biomarkers
0
Neurofilament Proteins
0
Oligonucleotides
0
neurofilament protein L
0
nusinersen
5Z9SP3X666
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2129-2136Subventions
Organisme : Vetenskapsrådet
ID : NA
Organisme : Knut och Alice Wallenbergs Stiftelse
ID : NA
Organisme : Torsten Söderbergs Stiftelse
ID : NA
Organisme : FP7 Ideas: European Research Council
ID : 681712
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