2026-07-17T21:02:33Z https://api.figshare.com/v2/oai
oai:figshare.com:article/32825378 2026-06-29T14:39:00Z category_24733 category_24739 portal_549 item_type_7 month_year_06_2026
10.5522/04/32825378.v1 https://figshare.com/articles/presentation/Clemastine_as_remyelinating_treatment_in_patients_with_multiple_sclerosis_and_internuclear_ophthalmoplegia/32825378 https://ndownloader.figshare.com/files/66074759 N. Hof, Sam Sam N. Hof 0000-0002-0453-6449 Petzold, Axel Axel Petzold 0000-0002-0344-9749 <![CDATA[Clemastine as remyelinating treatment in patients with multiple sclerosis and internuclear ophthalmoplegia]]> Central nervous system Neurology and neuromuscular diseases Randomised Controlled Trails RCT multiple sclerosis internuclear ophthalmoparesis internuclear ophthalmoplegia INO clemastine fumarate Clemastine Remyelination 2026-06-29 2026-06-29 Presentation 2026 University College London Clemastine as remyelinating treatment in patients with multiple sclerosis and internuclear ophthalmoplegia


Sam.N. Hof 1,2, Daan J. de Jong1,2, P.C.G. Molenaar1,2, J.W.R. Twisk3, L.J. van Rijn4,5, B.M.J. Uitdehaag1,2, A. Petzold1,6


1 MS Center and Neuro-ophthalmology Expertise Center Amsterdam, Amsterdam UMC location Vrije Universiteit Amsterdam, Neurology, De Boelelaan 1117, Amsterdam, The Netherlands.

2 Amsterdam Neuroscience, Neuroinfection & -inflammation, Amsterdam, The Netherlands

3 Department of Epidemiology and Data Science, Amsterdam UMC, Amsterdam, The Netherlands.

4 Neuro-ophthalmology Expertise Center Amsterdam, Amsterdam UMC location Vrije Universiteit Amsterdam, Ophthalmology, De Boelelaan 1117, Amsterdam, The Netherlands.

5 Onze Lieve Vrouwe Gasthuis, Ophthalmology, Amsterdam, The Netherlands.

6The National Hospital for Neurology and Neurosurgery, Moorfields Eye Hospital and the Queen Square Institute of Neurology, UCL, London, United Kingdom.


Introduction

Remyelination failure contributes to disability and disease progression in multiple sclerosis (MS). Clemastine has shown promise for therapeutic remyelination in optic neuropathy, but its efficacy in other neural pathways remains uncertain. Brainstem lesions cause internuclear ophthalmoplegia (INO) in 25% of people with MS, and INO can transiently improve with fampridine. We investigated whether clemastine promotes brainstem remyelination and evaluated fampridine response as a remyelination predictor.

Methods

In this RCT, 47 people with MS and INO received 4 mg clemastine or placebo twice daily for 6 months. Horizontal saccades conjugacy, a measure of brainstem myelination, was quantified by infrared oculography at baseline, 3, 6, 12, 24 and 36 months. The primary outcome measure was the Versional Dysconjugacy Index (VDI). Before randomisation, participants underwent a 10 mg fampridine challenge. Those with VDI improvement were classified as responders and likely remyelinators. Secondary outcomes included other eye-movement parameters, OCT, visual acuity, disability, cognition and patient-reported outcomes.

Results

The trial ended on 15-Aug-2025. Positive fampridine response was observed in 23 subjects (49%), with a balanced distribution between clemastine (n=12) and placebo (n=11) groups. Fampridine response was associated with VDI improvement over time (p=0.004). Between-group differences were observed in the primary and several of the secondary outcome measures. Full efficacy data will be presented.

Conclusion

Inclusion of people with INO expands on previous studies on optic neuropathy and provides a platform to study central nervous system remyelination within the brainstem. Selecting for likely remyelinators through fampridine response is feasible and may strengthen future remyelination trials.


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