Antihistamines offer promise for myelin repair in multiple sclerosis

summary: A new study identifies the over-the-counter antihistamine clemastine as an effective drug for brain repair, paving the way for a potential treatment for multiple sclerosis (MS). Using newly developed MRI scanning technology, scientists were able to observe and measure the effects of clemastine on myelin levels in the brain.

This study provides the first documented example of brain repair in chronic neurological conditions by MRI. These results are expected to set the standard for future research on myelin remodeling therapies.

Important facts:

1. Clemastine, an over-the-counter antihistamine, has been identified as a potential treatment for MS with an observed increase in myelin water fraction indicative of myelin repair.
2. Using a proprietary MRI technology, we measure changes in myelin levels before and after drug administration, setting a new standard for tracking myelin recovery.
3. Beyond its potential effects on multiple sclerosis, clemastine is also being explored for use in treating brain injury in premature infants who often experience myelin damage.

sauce: UCSF

A decade after UC San Francisco scientists identified an over-the-counter antihistamine as a treatment for multiple sclerosis, researchers developed an approach to measure the drug’s effectiveness in repairing the brain It has also enabled us to evaluate future treatments for this devastating disease.

Researchers led by physician and scientist Ali Green, M.D., who along with neuroscientist Dr. Jonah Chang, first identified clemastine as a potential treatment for MS, used MRI scans to show that The effects on the brains of 50 participants were studied. clinical research.

of MS, the patient loses myelin, the protective insulator around the nerve fibers. This loss of myelin causes nerve signal delays, leading to weakness, spasticity, decreased vision, cognitive decline, and other symptoms.

In the brain, water trapped between the thin layers of myelin that wraps nerve fibers cannot move freely like water floating between brain cells.

This unique property of myelin allows imaging specialists to compare differences in myelin levels before and after drug administration by measuring the so-called myelin water content, the ratio of myelin water to total water in the brain. We were able to develop the technology. organization.

In their study, published May 8, 2023, PNASresearchers found that MS patients treated with clemastine experienced a modest increase in myelin water, indicative of myelin repair.

They also demonstrated that myelin water fractionation techniques could be used to track myelin recovery if the focus was on the right part of the brain.

“This is the first MRI-documented example of brain repair for a chronic neurological disease,” said Green, medical director of the UCSF Center for Multiple Sclerosis and Neuroinflammation and member of the Weill Institute for Neuroscience. Stated.

“This study provides the first direct, biologically validated, image-based evidence of clemastine-induced myelin repair. prize.”

Increased myelin even after stopping the drug

In this study, MS patients 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 for three to five months.

Using myelin water fraction as a biomarker, the researchers found that myelin water increased in the first group after participants were given the drug and continued to increase after clemastine was discontinued.

In the second group, a decrease in myelin water was seen in the first part of the study under placebo and a rebound after participants were given clemastine.

The findings support findings from a previous study of the same 50 patients, which showed that anti-allergy medications may reduce delayed nerve signaling and reduce symptoms. be.

In the current study, the researchers looked at the corpus callosum, a region of the brain with high myelin content that connects the right and left hemispheres.

They found that significant repair occurred outside the visible lesions typically associated with MS. This highlights the need to focus on myelin repair beyond these lesion sites.

Clemastine works in this situation by stimulating the differentiation of stem cells that make myelin. This makes the drug a generation ahead of existing MS treatments that work by weakening the immune system, reducing inflammation and reducing the risk of relapses. However, this is still not ideal and hydration measurements have become an important tool for developing better treatments.

“Clemastine is only partially effective at the doses we have available,” says Green, who is also a neuro-ophthalmologist and director of the Department of Neuroimmunology and Glial Biology at UCSF Neurology.

“It can have sedative effects, which may be particularly undesirable for MS patients. We hope that better treatments will be developed, but clemastine can remyelinate It has proven to be a tool that shows that

Future proposed studies will explore the potential of clemastine in the treatment of brain injury in premature infants who often experience myelin damage.

Bridget Ostrem, M.D., a pediatric neurologist at the University of California, San Francisco Benioff Children’s Hospital, is now initiating the first clinical trial testing clemastine to treat this debilitating and disabling condition. is seeking approval from the Food and Drug Administration.

About this neuropharmacology and multiple sclerosis research news

author: Ali Green
sauce: UCSF
contact: Ali Green – UCSF
image: Image credited to Neuroscience News

Original research: open access.
“MWF of the corpus callosum is a reliable measure of remyelination: results of the ReBUILD studyby Ali Green et al. PNAS

overview

MWF of the corpus callosum is a reliable measure of remyelination: results of the ReBUILD study

Myelin repair is an unrealized therapeutic goal in the treatment of multiple sclerosis (MS). There is still uncertainty about the optimal technique for assessing therapeutic efficacy, and imaging biomarkers are needed to measure and corroborate myelin restoration.

We analyzed myelin water fraction imaging from ReBUILD, a double-blind, randomized, placebo-controlled (delayed treatment) remyelination trial, and showed that VEP latency was significantly reduced in patients with MS. .

We focused on myelin-rich brain regions. Two groups of 50 MS subjects underwent 3T MRI at baseline and at months 3 and 5.

Half of the cohort was randomly assigned to receive treatment from baseline to 3 months, and the other half received treatment from 3 months to 5 months after baseline. We calculated the changes in myelin water content that occur in normal-appearing corpus callosum white matter, optic radiation, and corticospinal tracts.

An increase in the myelin water fraction was noted in normal-appearing white matter of the corpus callosum in response to administration of the remyelination therapeutic drug clemastine.

This study provides direct, biologically validated, image-based evidence of medically-induced myelin repair. Moreover, our study strongly suggests that significant myelin repair is occurring outside the lesion.

We therefore propose the myelin water fraction within the normal-appearing white matter of the corpus callosum as a biomarker for clinical trials examining remyelination.