How an allergy therapy ended up in the MS field
The team’s choice of compound was not random. Earlier screening of compounds approved for other diseases showed that clemastine fumarate activates oligodendrocyte progenitor cells. These are cells involved in producing and wrapping myelin around nerve cell axons, or long, slender projections of neurons.
Researchers confirmed this finding in lab-grown cells and animals with myelin damage before deciding to test it in patients with chronic neuron 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,” said Dr. Jonah R. Chan, a Debbie and Andy Rachleff Distinguished Professor of Neurology at UC-San Francisco.
“Intuitively, if myelin damage is new, the chance of repair is strong,” said Chan, the study’s senior author. “In the patients in our trial the disease had gone on for years.” But “we still saw strong evidence of repair” with clemastine fumarate, he said.
Measuring neuron speed
The team recruited 50 patients with chronic damage to their optic nerve for their study. They used a cross-over design to improve its statistical power.
Participants were split into two groups. One received clemastine fumarate for 90 days and then a placebo for 60 days. The other received a placebo first and then the drug. Then the groups switched, and the procedure was repeated. Neither patients nor the physicians in the study knew which group patients belonged to.
To assess potential effects of the drug, researchers measured what is known as visual-evoked potentials, or how fast neurons that govern sight fire in response to changes in light.
They used scalp electrodes to measure signals in the part of the brain that oversees vision. This area is located in the back of the brain. In people with optic nerve damage, it takes longer for a nerve signal — a response to a flickering pattern on a screen — to travel between the eye and the back of the brain.
Researchers discovered that the speed of the signals was significantly improved in the group that started with clemastine fumarate. The effect persisted after the group was put on a placebo for two months, suggesting that the improved neuronal function was long-lasting.
The team also measured participants’ ability to detect changes in visual contrast. It improved after the treatment, but not enough to reach statistical significance.
Restoration of myelin is called remyelination. The team failed to prove it had occurred because “we still don’t have imaging methods that have been proven to be able to detect remyelination in humans,” Chan said.
But the team said myelin regeneration was the only plausible explanation for the results. That’s because it’s well-known that myelin speeds up nerve signals.
We are sorry that this post was not useful for you!
Let us improve this post!
Tell us how we can improve this post?