Antihistamine Repurposed for Remyelination in Phase 2 Trial from UCSF
The University of California, San Francisco (UCSF) initiated a clinical trial to evaluate the antihistamine clemastine fumarate, manufactured by Novartis as Tavist, for its efficacy in treating multiple sclerosis patients. The laboratory of Dr. Jonah Chan, a professor of neurology at UCSF, used a high-throughput method to identify Tavist and seven other Food and Drug Administration-approved medicines as potentially efficacious for multiple sclerosis therapy.
“A major unmet need in the development of therapeutics for repair in multiple sclerosis has been the ability to screen compounds in a high-throughput manner,” said Dr. Chan in a news report. Along with lead author Feng Mei and collaborators from UCSF, Third Military Medical University in China, University of Cambridge, and Trianja Technologies in Texas, Dr. Chan published the team’s research in Nature.
As described in the paper, the research team screened 1,000 bioactive molecules in a unique platform called “binary indicant for myelination using micropillars arrays.” Among the molecules, eight had a positive effect on oligodendrocyte precursor cell (the myelinating cells of the brain) differentiation and remyelination. All eight worked through muscarinic receptors on oligodendrocyte precursors, but of the molecules tested, clemastine was the most potent.
After identifying the effects of clemastine on in vitro oligodendrocytes, the team moved on to in vivo studies to treat mice with spinal cord lesions. Just as in multiple sclerosis myelin is damaged, so to in spinal cord injuries is myelin damaged. Clemastine had a remyelinating effect on mice treated with the compound.
To see how clemastine affects multiple sclerosis patients and determine dosing requirements, clinical trials have been initiated, and the current Phase 2 trial is still enrolling patients. Researchers are primarily interested in the effects of clemastine on vision, but tolerability and disability changes are outcome measures, as well.
Outcome measures will be assessed at three and five months after taking a baseline at the beginning of treatment. Fifty patients will be treated for a total of five months in the crossover study. For the first three months, patients will receive either a 4 mg Tavist (clemastine fumarate) tablet or placebo twice daily, and for the following two months, patients will receive the alternate treatment (placebo or Tavist).
In addition to the clinical trial, a company focused on regrowing myelin has started on the basis of Dr. Chan’s high-throughput method. Roche, which is the parent company of Genetech, and Versant Ventures, a Menlo Park-based venture capital firm, formed Inception 5 one month ago. Inception 5 is among a number of companies who have begun to focus on remyelination rather than only soothing inflammation and stopping myelin erosion.
Dr. Chan’s research was backed by donations to UCSF’s MS Research Group, UCSF’s Clinical and Translational Science Institute, and the National Multiple Sclerosis Society. Although the study shows promise for Tavist as a multiple sclerosis treatment, it is only approved as an antihistamine, and multiple sclerosis patients are urged not to self-medicate with Tavist because its effects are unknown for multiple sclerosis.