A decade after an over-the-counter antihistamine named clemastine was identified by scientists at UC San Francisco as a potential treatment for multiple sclerosis (MS), researchers have now developed a method to assess the drug’s effectiveness in repairing the brain, a breakthrough that could pave the way for evaluating future MS therapies.
In the study led by Dr. Ari Green and neuroscientist Jonah Chan, Ph.D., who initially identified clemastine’s therapeutic potential, 50 participants underwent MRI scans to investigate the drug’s effect on the brain.
MS is characterized by the loss of myelin, the protective layer around nerve fibers. Myelin loss leads to delayed nerve signals, which can cause symptoms such as vision loss, cognitive slowing, weakness, and spasticity.
The scientists made use of a unique characteristic of myelin, where water trapped between the thin layers of myelin that wrap nerve fibers behaves differently than water between brain cells.
This property helped the team develop a technique to measure the difference in myelin levels before and after the drug was given, referred to as the myelin water fraction (the ratio of myelin water to total water content in brain tissue).
The researchers found that patients treated with clemastine showed minor increases in myelin water, indicating myelin repair.
Additionally, the myelin water fraction technique could be used to track myelin recovery when focused on the right areas of the brain. Their findings were published in the PNAS journal on May 8, 2023.
In the ReBUILD trial, MS patients were divided into two groups, with one receiving clemastine for the first three months and the other receiving the drug only during the third to the fifth month.
Using the myelin water fraction as a biomarker, researchers found myelin water continued to increase even after clemastine was stopped in the first group, while the second group showed a rebound in myelin water after they began receiving clemastine.
Clemastine works by stimulating the differentiation of stem cells that make myelin, setting it apart from existing MS drugs that primarily work by reducing the activity of the immune system, and therefore, inflammation and risk of relapse.
However, the drug is only partially effective and can cause sedation, which can be particularly problematic for MS patients.
Therefore, the new myelin water fraction measurement technique could be key in the development of better therapeutics.
Future research will explore clemastine’s potential in treating brain injury in premature infants, who often experience myelin damage.
Dr. Bridget Ostrem, a pediatric neurologist at UCSF Benioff Children’s Hospitals, is seeking approval from the FDA to conduct the first clinical trial testing clemastine for this condition.
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The study was published in PNAS.
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