A decade after UC San Francisco scientists identified an over-the-counter antihistamine as a treatment for multiple sclerosis, researchers have developed an approach to measure the drug’s effectiveness in repairing the brain, making it possible to also assess future therapies for the devastating disorder.
The researchers first identified clemastine as a potential MS therapy, and used MRI scans to study the drug’s impact on the brain of 50 participants in a clinical study.
In MS, patients lose myelin, the protective insulation around nerve fibers. This myelin loss triggers delays in nerve signals, leading to weakness and spasticity, vision loss, cognitive slowing and other symptoms.
In the study, patients with MS who enrolled in the ReBUILD trial were divided into two groups: the first group received clemastine for the first three months of the study and the second group received clemastine only in months three to five. Using the myelin water fraction as a biomarker, the researchers found that myelin water increased in the first group after participants received the drug and continued to increase after clemastine was stopped. In the second group, the myelin water fraction showed decreases in myelin water in the first portion of the study, under the placebo, and a rebound after participants received clemastine.
In their study, the researchers found that patients with MS who were treated with clemastine experienced modest increases in myelin water, indicating myelin repair. They also proved that the myelin water fraction technique, when focused on the right parts of the brain, could be used to track myelin recovery.
“This is the first example of brain repair being documented on MRI for a chronic neurological condition,” said Green, medical director of the UCSF Multiple Sclerosis and Neuroinflammation Center. “The study provides the first direct, biologically validated, imaging-based evidence of myelin repair induced by clemastine. This will set the standard for future research into remyelinating therapies.”
Clemastine works in this setting by stimulating the differentiation of myelin-making stem cells. This places the medication a generation ahead of existing MS drugs that work by dampening the activity of the immune system, calming inflammation and reducing the risk of relapse. It still isn’t ideal, though, making the water fraction measurement an important tool in developing better therapeutics.
Eduardo Caverzasi, Nico Papinutto, Christian Cordano, Gina Kirkish, Tristan J. Gundel, Alyssa Zhu, Amit Vijay Akula, W. John Boscardin, Heiko Neeb, Roland G. Henry, Jonah R. Chan, Ari J. Green. MWF of the corpus callosum is a robust measure of remyelination: Results from the ReBUILD trial. Proceedings of the National Academy of Sciences, 2023; 120 (20) DOI: 10.1073/pnas.2217635120
University of California – San Francisco. “Can this medication reverse MS? Brain biomarker shows it can: Research identifies hallmark of disease repair for use in future therapies.” ScienceDaily. ScienceDaily, 12 June 2023. <www.sciencedaily.com/releases/2023/06/230612200436.htm>.
Photo by Max Bender