A group of researchers at UC San Francisco has made significant progress in measuring the effectiveness of an over-the-counter antihistamine as a treatment for multiple sclerosis (MS). This development not only allows them to assess the drug’s impact on repairing the brain but also paves the way for future therapies for this devastating disorder.
The team, led by physician-scientist Dr. Ari Green and neuroscientist Dr. Jonah Chan, conducted a clinical study involving 50 participants with MS. They used MRI scans to examine how the drug, known as clemastine, affected the participants’ brains.
In MS, patients experience the loss of myelin, which is the protective coating around nerve fibers. This loss leads to delays in nerve signals, resulting in weakness, spasticity, vision loss, cognitive impairments, and other symptoms.
The researchers discovered that the water trapped between the thin layers of myelin in the brain does not move as freely as the water found between brain cells. This unique property of myelin enabled them to develop a technique to measure the difference in myelin levels before and after administering the drug. They called this measurement the “myelin water fraction,” which represents the ratio of myelin water to the total water content in brain tissue.
Their study, published on May 8, 2023, in PNAS, revealed that MS patients treated with clemastine experienced slight increases in myelin water, indicating potential myelin repair. Moreover, the researchers demonstrated that by focusing on specific areas of the brain, the myelin water fraction technique could be used to track myelin recovery.
Dr. Green, the medical director of the UCSF Multiple Sclerosis and Neuroinflammation Center and a member of the Weill Institute for Neurosciences, stated, “This is the first example of brain repair being documented on MRI for a chronic neurological condition. 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.”
Interestingly, the study also revealed that myelin water continued to increase even after stopping the medication. The researchers divided the participants into two groups: the first group received clemastine for the first three months, while the second group received it only from months three to five. By using the myelin water fraction as a biomarker, they observed an increase in myelin water in the first group, which continued even after the drug was discontinued. In the second group, there was a decrease in myelin water during the placebo period and a rebound after the participants received clemastine.
These findings support the results of a previous study involving the same 50 patients, which showed that the allergy medication reduced delays in nerve signaling, potentially alleviating MS symptoms.
The researchers specifically examined the corpus callosum, a brain region with a high concentration of myelin that connects the left and right hemispheres. They found significant repair occurring outside the typical visible lesions associated with MS. This highlights the importance of focusing on myelin repair beyond these lesion sites.
Clemastine works by stimulating the differentiation of myelin-producing stem cells. This sets it apart from existing MS drugs, which primarily work by suppressing immune system activity, reducing inflammation, and minimizing the risk of relapse. However, clemastine is not without its limitations. It can cause sedation, which may be particularly undesirable for MS patients. The researchers remain hopeful that better medications will be developed, but for now, clemastine has demonstrated its potential for promoting remyelination.
In the future, researchers plan to explore the potential of clemastine in treating brain injuries in premature infants, who often experience myelin damage. Dr. Bridget Ostrem, a pediatric neurologist from UCSF Benioff Children’s Hospitals, is currently seeking approval from the Food and Drug Administration to conduct the first clinical trial testing clemastine for this debilitating condition.
