A decade after UC San Francisco scientists identified an over-the-counter antihistamine as a treatment for multiple sclerosisresearchers have developed an approach to measure the drug’s effectiveness in brain repair, making it possible to also evaluate future therapies for the devastating disorder.
The researchers, led by physician-scientist Ari Green, MD, who together with neuroscientist Jonah Chan, Ph.D., first identified clemastine as a potential MS therapy, used MRI scans to study the impact of drug on the brains of 50 participants in a clinical trial study.
The results of research have been posted on PNAS.
Multiple sclerosis: here is the report of the new research
In multiple sclerosis, 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 brain, water trapped between the thin layers of myelin that wrap around nerve fibers can’t move as freely as the water floating between brain cells. This unique property of myelin has allowed imaging experts to develop a technique to compare the difference in myelin levels before and after drug administration by measuring the so-called aqueous fraction of myelin, or the ratio of myelin water to the content total water in brain tissue.
In their study the researchers found that patients with Multiple Sclerosis treated with clemastine experienced a modest increase in myelin water, indicating myelin repair. Scientists also demonstrated that the myelin aqueous fraction technique, when focused on the right parts of the brain, could be used to monitor myelin recovery.
“This is the first example of MRI-documented brain repair for a chronic neurological condition,” said Green, medical director of UCSF’s Center for Multiple Sclerosis and Neuroinflammation and a fellow at the Weill Institute for Neurosciences. “The study provides the first direct, biologically validated, imaging-based evidence of clemastine-induced myelin repair. This will set the standard for future research into remyelinating therapies.”
In the study, patients with multiple sclerosis enrolled in the ReBUILD study 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 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, myelin water showed decreases in the first part of the study, under the placebo, and a rebound after participants received clemastine.
The findings confirm findings from a previous study with the same 50 patients that found that allergy medication reduced delayed nerve signaling, potentially easing symptoms.
In the current study, the researchers looked at the corpus callosum, a brain region with a high myelin content that connects the left and right hemispheres. They found that significant repair occurred outside the visible lesions typically associated with multiple sclerosis. This underscores the need to focus on myelin repair beyond these injury sites.
Clemastine works in this context by stimulating the differentiation of myelin-producing stem cells. This puts the drug a generation ahead of existing multiple sclerosis drugs that work by dampening the activity of the immune system, calming inflammation and reducing the risk of relapse. However, it is still not ideal, making water fraction measurement an important tool for developing better therapies.
“Clemastine may be only partially effective at doses that we can use,” said Green, who is also a neuro-ophthalmologist and chief of the Division of Neuroimmunology and Glial Biology in the UCSF Department of Neurology. “It can be sedative, which can be particularly undesirable in patients with Multiple Sclerosis. Hopefully better drugs will be developed, but clemastine has proven to be the tool to prove that remyelination is possible.”
Proposed future research will examine clemastine’s potential in treating brain injury in premature infants, who often experience damage to their myelin. Pediatric neurologist Bridget Ostrem, MD, Ph.D., of UCSF Benioff Children’s Hospitals, is currently seeking approval from the Food and Drug Administration to initiate the first clinical trial of clemastine for the treatment of this debilitating and disabling condition.
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