VANCOUVER—Among people with multiple sclerosis (MS) and chronic demyelinating optic neuropathy, clemastine fumarate reduces visual evoked potential latency delay, a putative biomarker for remyelination, according to a phase II study presented at the 68th Annual Meeting of the American Academy of Neurology.
"This is the first randomized controlled trial documenting efficacy for a candidate remyelinating agent in MS," said Ari Green, MD, Assistant Clinical Director of the Multiple Sclerosis Center at the University of California San Francisco (UCSF), and colleagues.
Ari Green, MD
Investigators at UCSF identified clemastine fumarate, an antihistamine that is available over the counter, as a potential remyelinating agent using an in vitro micropillar screen. In an animal model, the agent led to robust remyelination and appeared to protect axons, said Dr. Green.
To assess the efficacy of clemastine fumarate for remyelination in patients with MS and chronic optic neuropathy, Dr. Green and colleagues conducted a double-blind, randomized, placebo-controlled, crossover study.
They enrolled 50 participants who had a delay in transmission time greater than 118 ms in at least one eye. Patients had an average age of 40, Expanded Disability Status Scale score of 2.1, and disease duration of 5.1 years. The study period was 150 days.
Patients were grouped into two treatment arms. For the first treatment period, 25 patients received oral clemastine fumarate and 25 patients received placebo twice daily. The primary efficacy end point was change in latency delay on visual evoked potential.
Visual evoked potential latency delay was reduced by 1.9 ms per eye for the period on treatment. A strong trend for improvement of the secondary end point of low contrast visual acuity also was observed. Clemastine treatment was associated with mild worsening of fatigue on the Multidimensional Assessment of Fatigue, however.
Among patients who first received clemastine, the treatment effect was sustained "even into the second epoch, suggesting that we were in fact having a remyelinating effect, and not just a transient effect on ion channels," Dr. Green said.
Larger studies are needed before doctors can recommend clemastine fumarate for people with MS, Dr. Green said. New medications are in development, and researchers aim to improve the targeting and reduce the side effects from these drugs.
"While the improvement in vision appears modest, this study is promising because it is the first time a drug has been shown to possibly reverse the damage done by MS," said Dr. Green. "Findings are preliminary, but this study provides a framework for future MS repair studies and will hopefully herald discoveries that will enhance the brain's innate capacity for repair."