Results from a phase 2 clinical trial published by The Lancet
suggest that an OTC antihistamine may repair nervous system function in patients with multiple sclerosis (MS).
In previous laboratory studies, the antihistamine was thought to restore nerve cell signaling by repairing damage to the myelin, a hallmark of MS.
In the new study, the authors explored the effects of clemastine fumarate, an antihistamine that was approved as an allergy drug in the 1970s and has been available as an OTC and generic treatment since the 1990s.
“To the best of our knowledge this is the first time a therapy has been able to reverse deficits caused by MS,” said the trial’s principal investigator, Ari Green, MD. “It’s not a cure, but it’s a first step towards restoring brain function to the millions who are affected by this chronic, debilitating disease.”
These phase 2 findings are the first to show that the allergy drug can restore human brain function damaged by MS, according to the authors. The results are especially significant because participants had established myelin damage.
“People thought we were absolutely crazy to launch this trial, because they thought that only in newly diagnosed cases could a drug like this be effective – intuitively, if myelin damage is new, the chance of repair is strong,” said researcher Jonah R. Chan, PhD. “In the patients in our trial the disease had gone on for years, but we still saw strong evidence of repair.”
As myelin damage is sustained over the course of the disease, neurons have reduced ability to transmit electrical signals between nerves, which leads to the loss of vision, weakness, walking, and problems with coordination and balance. While current therapies
aim to prevent additional injury, none can repair myelin damage.
In mouse models of MS, clemastine fumarate was observed to regenerate myelin and restore neuron function.
Since vision is the first to be affected by MS and there are tools that can measure the speed of neural transmission in the brain related to vision, the authors used vision evoked potentials (VEPs) to evaluate the drug.
Included in the trial were 50 patients with relapsing MS whose VEPs showed poor neural transmission at baseline. Electrodes were placed over the brain’s visual areas and patients were exposed to flickering patterns. The electrodes tracked how long it took for the signal to travel from the retina to the visual area at the back of the brain, according to the study.
Patients then received clemastine fumarate or placebo for 90 days and then switched treatment for the next 90 days, which allowed the authors to better analyze the results for the allergy drug.
The investigators found that when patients were taking the drug, signaling from the eye to the back of the brain was significantly accelerated compared with baseline, according to the study.
Importantly, the effect lasted even when patients switched to placebo, which suggests a long-lasting repair of the myelin.
The researchers said they were unable to observe the remyelination process in humans due to a lack of advanced MRI techniques.
“We still don’t have imaging methods that have been proven to be able to detect remyelination in humans,” Dr Chan said.
In addition to preclinical findings, these results suggest that clemastine fumarate induces myelin repair and may be a promising therapy for patients with MS.
“This is the first step in a long process,” Dr Green said. “By no means do we want to suggest that this is a cure-all. We want to ground-truth myelination metrics – we’re designing the crucible that’s going to be used to test any future method for detecting remyelination.”