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Biomarker Report from the Phase II Lamotrigine Trial in Secondary Progressive MS - Neurofilament as a Surrogate of Disease Progression

Gnanapavan, S; Grant, D; Morant, S; Furby, J; Hayton, T; Teunissen, CE; Leoni, V; ... Giovannoni, G; + view all (2013) Biomarker Report from the Phase II Lamotrigine Trial in Secondary Progressive MS - Neurofilament as a Surrogate of Disease Progression. PLoS One , 8 (8) , Article e70019. 10.1371/journal.pone.0070019. Green open access

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Abstract

Objective Lamotrigine trial in SPMS was a randomised control trial to assess whether partial blockade of sodium channels has a neuroprotective effect. The current study was an additional study to investigate the value of neurofilament (NfH) and other biomarkers in predicting prognosis and/or response to treatment. Methods SPMS patients who attended the NHNN or the Royal Free Hospital, UK, eligible for inclusion were invited to participate in the biomarker study. Primary outcome was whether lamotrigine would significantly reduce detectable serum NfH at 0-12, 12–24 and 0–24 months compared to placebo. Other serum/plasma and CSF biomarkers were also explored. Results Treatment effect by comparing absolute changes in NfH between the lamotrigine and placebo group showed no difference, however based on serum lamotrigine adherence there was significant decline in NfH (NfH 12–24 months p = 0.043, Nfh 0–24 months p = 0.023). Serum NfH correlated with disability: walking times, 9-HPT (non-dominant hand), PASAT, z-score, MSIS-29 (psychological) and EDSS and MRI cerebral atrophy and MTR. Other biomarkers explored in this study were not found to be significantly associated, aside from that of plasma osteopontin. Conclusions The relations between NfH and clinical scores of disability and MRI measures of atrophy and disease burden support NfH being a potential surrogate endpoint complementing MRI in neuroprotective trials and sample sizes for such trials are presented here. We did not observe a reduction in NfH levels between the Lamotrigine and placebo arms, however, the reduction in serum NfH levels based on lamotrigine adherence points to a possible neuroprotective effect of lamotrigine on axonal degeneration.

Type: Article
Title: Biomarker Report from the Phase II Lamotrigine Trial in Secondary Progressive MS - Neurofilament as a Surrogate of Disease Progression
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0070019
Publisher version: http://dx.doi.org/10.1371/journal.pone.0070019
Language: English
Additional information: © 2013 Gnanapavan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3731296
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/1402914
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