Myelin Regeneration Achieved in Mouse Model of MS

Myelin Regeneration Achieved in Mouse Model of MS

Therapies aimed at regenerating the myelin sheath can work to restore proper brain activity and may be a viable way of treating multiple sclerosis (MS), according to researchers at the University of California San Francisco.

In the study, “Accelerated Remyelination During Inflammatory Demyelination Prevents Axonal Loss And Improves Functional Recovery,” published in the journal eLife, researchers used mice with MS to understand exactly how remyelination could be triggered.

The myelin sheath — a coating made of myelin proteins that protects neurons and enhances the transmission of electrical impulses between them — is progressively lost in patients with MS, due to aberrant immune system attacks that destroy myelin. Myelin degeneration destabilizes neuronal function and ultimately leads to nerve cell death, contributing to disease progression and disability in MS patients. Many therapies have been developed in an attempt to promote remyelination and rescue neuronal function, but results did not support their viability.

“The key thing we learned from this study is that if we can design therapies that promote remyelination — especially when myelin has been damaged by inflammation as it is in MS — we can prevent neuronal loss and restore function,” the senior author of the study, Jonah Chan, PhD, said in a news release. “This is something I and other investigators have wanted to promise to MS patients, but we simply didn’t have the data.”

Researchers injected mice with a protein found in the myelin sheath that triggers a form of MS, called experimental autoimmune encephalomyelitis (EAE), which has an inflammatory response with physiological and behavioral consequences similar to those seen in human patients. At the same time, the mice also received an injection of clemastine, a drug the team had previously shown to be capable of promoting remyelination. This drug activates a group of proteins, called the muscarinic receptors, that are present in the cells that produce myelin, the oligodendrocytes.

They observed that mice treated with clemastine had less severe MS-like symptoms, and that a certain degree of remyelination occurred in their brain and spinal cord, which protected neurons from degeneration.

Because the researchers did not know the exact mechanism of action of clemastine, they tested the drug on several different receptors to identify which ones were affected by the treatment. They then identified the M1 receptors as one of the targets of clemastine, and observed that blocking these proteins induced the production of more oligodendrocytes, which is critical for remyelination.

However, because clemastine also targets other, similar receptors, and no drug is known to selectively block the M1 receptors, researchers used genetic tools to deplete the mouse brain of these receptors. In these animals, the team observed significant remyelination and reduced neuronal death, including restored neuronal function even when EAE inflammation was at its maximum. These results support the idea that inhibition of M1 receptors promotes remyelination by increasing the number of oligodendrocytes in the brain.

“Now that we’ve shown we can promote repair during the peak inflammation period, and that new myelin may remain stable,” Chan said, “we can now say to MS patients that focusing on this remyelination space has the potential to not only restore function, but to improve their quality of life.”

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Joana brings more than 8 years of academic research and experience as well as Scientific writing and editing to her role as a Science and Research writer. She also served as a Postdoctoral Researcher at the Center for Neuroscience and Cell Biology in Coimbra, Portugal, where she also received her PhD in Health Science and Technologies, with a specialty in Molecular and Cellular Biology.

30 comments

  1. Arrian Sabzvari says:

    I have MS 20+ years, would be extremely interested to expand my knowledge and potentially take part in any associated trials.

  2. Jeanine Shahin says:

    Clementine fumarate is an antihistamine available orally over the counter. There was a trial using Clementine fumarate in optic neuritis.

  3. Terri Magida says:

    I have MS for 20 yrs and my legs have gotten progressively worse the past 2 years. I would be willing to partake in clinical trials.

  4. Lynda Strecker says:

    I too would be interested in participating in a trial. This clemastine sounds promising. I’ve had ms for 23 yrs.and am really hoping that something like this will be offered as a healing option.

  5. Elyse Brown says:

    I’ve had MS for over 30 years. I was diagnosed in my early 20’s but had symptoms even as a child. I am mostly in a wheelchair when not using a rollator. I would definitely be interested in taking part of the human trials!! Hopefully, it won’t be long before this becomes available. Thanks to all of the researchers and all of the supporters that are trying to find a cure!

  6. Ian Robert Mackay says:

    my wife has said that she would take part.25 years on one stick ,then two sticks and then wheel chair .we are now at the pain and sleepy stage.
    if you want a ideal candidate she is the one,let us know where and when

  7. Harry Crawford says:

    I’m very interested in takin part in the human trials. Who do we contact and when can when start? I’ve had MS since 1999 with no issues until the past 5 years. It’s been affecting my legs pretty bad especially in the past 2 years. Please give all of us info and an opportunity to help you help us and others as well.

  8. Paul Ojakian says:

    My Father,my sister and my self all have Ms. My Dad had since passed but my sister and I are still here with MS. I too would like to take part in a study. My family also was part of the genetic study done by Stephen Hauser at UCSF where they found a gene that was common in all participating parties.

      • itasara says:

        Teresa, I’m not a researcher him patient with MS that reads a lot. I understanding is that MS is not like diabetes I which is directly inherited from one or two parents, but there is a genetic factor which is involved. There are apparently many other and factors like vitamin D deficiency or the area one lives in etc. My understanding is that there have been genes found and it’s all the factors line up in the right way and family members may have MS in common. This is another area where more research is probably needed.

  9. Harry Crawford says:

    Well i believe there are enough MS patients commenting on wanting to partake in a trial for this med. Lets get it going. We all want to get just a little bit of our life back. I’m willing to take a chance on whatever side effects might come my way. Why let the mice have all the fun.

  10. spiro says:

    Here’s the issue with this study. It states that clemastine would be effective during “peak inflammation”, i.e, only in RRMS. That means in progressive MS, whether SPMS or PPMS, with no inflammation, this would not have little or no effect.

  11. Bruce Pawlecki says:

    Having been Dx w/RRMs back in 8/2008, seeing liasions progress at every MRI,experiencing progressively worsening mobility iss
    I’m very interested particpating in another clinical trial

  12. Linda C. Cooper says:

    I am 58 and was diagnosed in 2000. Even though I thought it started showing signs in 1991 looking at hind sight. I am interested in a clinical study. Dr. Suzanne Gazda @ Neurological Institute of San Antonio is my Nuerologist.

  13. Lisa M. says:

    If it is true that researchers can “trigger a form of MS” in mice (“Researchers injected mice with a protein found in the myelin sheath that triggers a form of MS, called experimental autoimmune encephalomyelitis (EAE), which has an inflammatory response with physiological and behavioral consequences similar to those seen in human patients.”), might there be something telling about this process that would help us understand how MS develops in humans?? (i.e. Is MS “triggered” in us in a similar way?)

  14. E.B. Higgs says:

    I am ready and certainly willing to participate in any and all human trials looking to throw MS into the proverbial dustbin of time! Diagnosed with secondary-progressive MS in 1999 switching to ppms 6 years on.

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