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Monday, July 20, 2015

Antihistamine Repurposed for Remyelination in Phase 2 Trial from UCSF

RemyelinationThe 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.

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