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

Autor:	Abdelhak A; Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA., Cordano C; Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA., Boscardin WJ; Departments of Medicine and Epidemiology & Biostatistics, University of California at San Francisco, San Francisco, California, USA., Caverzasi E; Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA., Kuhle J; Multiple Sclerosis Centre, Neurology, Departments of Head, Spine and Neuromedicine, Biomedicine and Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.; Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), University Hospital and University of Basel, Basel, Switzerland., Chan B; Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA., Gelfand JM; Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA., Yiu HH; Department of Biology, University of Maryland, College Park, Maryland, USA., Oertel FC; Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA., Beaudry-Richard A; Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA., Condor Montes S; Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA., Oksenberg JR; Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA., Lario Lago A; Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA., Boxer A; Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA., Rojas-Martinez JC; Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA., Elahi FM; Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA., Chan JR; Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA., Green AJ; Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA agreen@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Journal of neurology, neurosurgery, and psychiatry [J Neurol Neurosurg Psychiatry] 2022 Jun 16. Date of Electronic Publication: 2022 Jun 16.
DOI:	10.1136/jnnp-2022-329221
Abstrakt:	Background: Chronic 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. Methods: Plasma 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. Results: NfL 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. Conclusions: In 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. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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