A common over-the-counter antihistamine showed evidence of remyelination in patients with multiple sclerosis (MS) in a double-blind, placebo-controlled trial.
The study showed that clemastine – at a dose just slightly higher than that approved for allergies – reduced the delay in transmission in the optic nerve seen in patients with MS and chronic demyelinating optic neuropathy.
“We are extremely excited about these results,” commented lead author Ari Green, MD, medical director of the MS Center at the University of California, San Francisco (UCSF). Medscape Medical News. “Our main message is that it seems possible to repair nerve cell damage in MS through remyelination. We have been taught that the brain cannot repair itself, but our results suggest that is not true. . This could have consequences for many other neurodegenerative diseases as well as MS. “
The results were released on April 12 ahead of their presentation at the upcoming 2016 American Academy of Neurology (AAN) annual meeting.
The phase 2 crossover study – reportedly the first randomized controlled trial documenting the efficacy of a candidate remyelinating agent in MS – compared oral clemastine twice daily to placebo in 50 patients with MS and neuropathy chronic demyelinating optic. The study period was 150 days.
The primary measure of effectiveness, visual evoked potential latency time (VEP; the signal transmission time from the retina to the visual cortex), was reduced by 1.9 msec / eye during the period. treatment with clemastine (P = 0.003).
Dr Green explained that the VEP records the speed of transmission in the optic nerve from visual stimulus to image processing in the visual cortex of the brain.
“Good myelination of the nerve allows the signal to travel faster. For example, in an unmyelinated fiber, the signal would travel at a speed of 1 m / s. In contrast, a myelinated fiber would transmit the signal at around 100 m / s. , 100 times faster. The demyelination seen in MS-related optic neuritis can delay transmission by 30 to 50 ms. Clemastine appears to restore some of this loss. “
The researchers also looked at a functional endpoint – low contrast visual acuity – and found a strong tendency for improvement, but this did not reach statistical significance (P = .089).
In terms of side effects, treatment with clemastine was associated with a slight worsening of fatigue on the Multidimensional Fatigue Rating Scale (P = .017).
Reflection of nerves throughout the CNS
Dr Green said that while this study focuses only on the optic nerve, it likely reflects what is happening throughout the central nervous system. “We are using vision as a method of testing the principle of remyelination. The optic nerve is an obvious starting point because it is logistically feasible. We believe, however, that it should reflect the condition of the nerve in general and acts as a marker of substitution for the rest of the CNS [central nervous system]. “
But he urged MS patients to be careful. “I don’t want to make any false promises, and I’m not advocating that MS patients take clemastine based on this study alone. But if they choose to do so, they should have the supervision of a doctor and preferably enroll in a study clinic. “
Clemastine has been identified as a potential remyelinating agent in a screening program developed by a team at UCSF led by Jonah Chan, PhD, using precursor cells of oligodendrocytes (the cells that make myelin).
“These oligodendrocyte precursor cells are present in the brain but do not appear to mature and produce oligodendrocytes,” explained Dr. Green. “We are looking for agents that stimulate precursor cells to differentiate into oligodendrocytes and produce new myelin to repair damaged neurons. Chan et al have tested many existing drugs and found that clemastine does just that.”
Researchers have identified a specific muscarinic receptor on which clemastine acts to cause this effect. “It is likely that the drug will only partially saturate the receptor, so we may not see the full effect,” Dr Green said.
But because clemastine acts on many other receptors as well, his group is studying the development of new agents that act specifically on this receptor, which may be more suitable for myelin repair. “We also know that there are other non-muscarinic receptors that appear to produce similar results, so there are some possibilities under investigation,” he added.
“The screening method identified the biology. We now need to refine that biology,” commented Dr Green.
Biogen is also developing a compound known as anti-LINGO, which has shown evidence of remyelination. Dr Green noted that the anti-LINGO study recently reported patients involved with a current episode of optic neuritis. “They therefore showed an acute action, whereas the patients in our study did not have a recent episode of optic neuritis and we therefore showed evidence of benefit in the chronic phase.”
Commenting on the study of Medscape Medical News, Lily Jung Henson, MD, chief of neurology, Piedmont Healthcare, Atlanta, Ga., Said, “This is really exciting preliminary news. The results seem to suggest that clemastine may be effective in remyelination, for which we have no no treatment. “
She warned that larger studies will be needed with patients treated for longer periods for confirmation. “Since clemastine is an anticholinergic, it will be interesting to see if it causes worsening of certain symptoms of MS, such as cognitive difficulties, urinary hesitation or constipation,” she added.
The study was funded by the University of California at San Francisco.
American Academy of Neurology (AAN) Annual Meeting 2016. Emerging Science Abstract 008. To be presented April 19, 2016.