Plasma neurofilament light chain levels suggest neuroaxonal stability following therapeutic remyelination in people with multiple sclerosis

BackgroundChronic demyelination is a major contributor to axonal vulnerability in multiple sclerosis (MS). Therefore, remyelination could provide a potent neuroprotective strategy. The ReBUILD trial was the first study showing evidence for successful remyelination following treatment with clemastine...

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Veröffentlicht in:Journal of neurology, neurosurgery and psychiatry Jg. 93; H. 9; S. 972 - 977
Hauptverfasser: Abdelhak, Ahmed, Cordano, Christian, Boscardin, W John, Caverzasi, Eduardo, Kuhle, Jens, Chan, Brandon, Gelfand, Jeffrey M, Yiu, Hao H, Oertel, Frederike C, Beaudry-Richard, Alexandra, Condor Montes, Shivany, Oksenberg, Jorge R, Lario Lago, Argentina, Boxer, Adam, Rojas-Martinez, Julio C, Elahi, Fanny M, Chan, Jonah R, Green, Ari J
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England BMJ Publishing Group Ltd 01.09.2022
BMJ Publishing Group LTD
Schlagworte:
Biomarkers
Body mass index
Creatinine
Magnetic resonance imaging
Multiple sclerosis
NEUROBIOLOGY
Plasma
Sample size
Variance analysis
United States > US
San Francisco California
California
MULTIPLE SCLEROSIS
NEUROBIOLOGY
ISSN:0022-3050, 1468-330X, 1468-330X
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Zusammenfassung:BackgroundChronic demyelination is a major contributor to axonal vulnerability in multiple sclerosis (MS). Therefore, remyelination could provide a potent neuroprotective strategy. The ReBUILD trial was the first study showing evidence for successful remyelination following treatment with clemastine in people with MS (pwMS) with no evidence of disease activity or progression (NEDAP). Whether remyelination was associated with neuroprotection remains unexplored.MethodsPlasma neurofilament light chain (NfL) levels were measured from ReBUILD trial’s participants. Mixed linear effect models were fit for individual patients, epoch and longitudinal measurements to compare NfL concentrations between samples collected during the active and placebo treatment period.ResultsNfL concentrations were 9.6% lower in samples collected during the active treatment with clemastine (n=53, geometric mean=6.33 pg/mL) compared to samples collected during treatment with placebo (n=73, 7.00 pg/mL) (B=−0.035 [−0.068 to −0.001], p=0.041). Applying age- and body mass index-standardised NfL Z-scores and percentiles revealed similar results (0.04 vs 0.35, and 27.5 vs 33.3, p=0.023 and 0.042, respectively). Higher NfL concentrations were associated with more delayed P100 latencies (B=1.33 [0.26 to 2.41], p=0.015). In addition, improvement of P100 latencies between visits was associated with a trend for lower NfL values (B=0.003 [−0.0004 to 0.007], p=0.081). Based on a Cohen’s d of 0.248, a future 1:1 parallel-arm placebo-controlled study using a remyelinating agent with comparable effect as clemastine would need 202 subjects per group to achieve 80% power.ConclusionsIn pwMS, treatment with the remyelinating agent clemastine was associated with a reduction of blood NfL, suggesting that neuroprotection is achievable and measurable with therapeutic remyelination.Trial registration number NCT02040298.
Bibliographie:Original research
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0022-3050
1468-330X
1468-330X
DOI:10.1136/jnnp-2022-329221