CONy16: MS Researchers Question Possible Long-term Benefits of Remyelination Therapies

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MS and CONy16

Multiple sclerosis was a main focus at the four-day 10th World Congress on Controversies in Neurology (CONy), in Lisbon, Portugal, that concluded on March 20. Among the topics of debate was demyelination as the disease’s main pathogenic precursor and the clinical potential of remyelination.

The debate, titled “Can we expect long-term clinical improvement through remyelination?” and hosted by David Leppert from Roche, in Basel, Switzerland, included the views of Abhijit Chaudhuri from Queen’s Hospital, U.K., and Olaf Stuve from the University of Texas Southwestern Medical Center. It focused on demyelination and neurodegeneration linked to clinical disability, and a possible combination of the two mechanisms.

Demyelinating plaques, with surrounding inflammation and neurodegeneration, are hallmarks common to all types of MS. Despite being one of the key pathological changes in the disease, a demyelination-specific autoimmune reaction has never been identified, and the precise cause for MS remains unknown, mainly due to the complexity of the disease.

Myelin loss leads to a progressive decrease of nerve conduction velocity, and to a higher predisposition of axons to neurodegeneration due to the lack of physical and metabolic support. Dr. Stuve’s argued that myelin damage and axonal loss are the core of neurological disability in MS, a position he supported by noting that axonal loss can be detected in the earliest stages of MS, and that brain atrophy, assessed by magnetic resonance imaging (MRI), is evident in MS patients with different disease phenotypes and degrees. Both mechanisms, in their different degrees of severity, are likely irreversible and, as such, he said, remyelination strategies are unlikely to show much efficacy in recovering MS patients’ neurological abilities.

Dr. Chaudhuri highlighted remyelination events, which are characteristic of relapsing-remitting MS. He noted that spontaneous remyelination in MS lesions is either limited to the lesions’ edge or occurs throughout the entire lesion region, forming the so-called “shadow plaques,” but these remyelinated plaques may become future targets of demyelination. Moreover, there is no evidence of positive correlation between the number of shadow plaques or early remyelination and better functional preservation in patients with any type of MS.

MS research has focused on the development of novel drugs targeting pathways that promote remyelination, but existing evidence suggests that none of these agents promote remyelination beyond the naturally occurring levels.

In light of this evidence, Dr. Chaudhuri argued that attempts at remyelination would be, at best, partial or incomplete, and this treatment strategy alone would not yield meaningful functional improvements or axonal rescue and reverse  neuronal loss. This failing would be even more evident if the theory that MS is primarily a neurodegenerative disease, and loss of myelin a secondary effect, was proven to be true. The scientist theorized that the benefit of remyelination would likely be improvement of nerve conduction, instead of grey and white matter protection from progressive MS pathology.

Dr. Chaudhuri concluded that, at this point, long-term clinical improvement from remyelination therapy is purely speculative, due to the lack of robust clinical data and the yet-to-be-identified appropriate imaging marker of remyelinating lesions in MS.

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  1. Liam says:

    The tone of Stuve and Chaudhuri’s arguments reek of conflict of interest. Both of these immunology researchers are quite cozy with Pharma companies who have no desire to find a cure for MS. Pharma is scared that remyelination therapies might just render their expensive ‘maintain em but keep em sick’ products useless. Be very skeptical.

    • Joan Quilter says:

      I agree. I’ve read so much about the benefits of remyelination, and how stem cell therapy (in one way or another) will, ultimately, help in this regard.

  2. jake says:

    How can you not see remyelination therapies as a positive move forward? Sure, the underlying process has to be addressed, but for those of us whose myelin is being stripped away… it is clearly a both/and proposition. Sidelining these efforts because they are incomplete is not in my best interest as a patient who is facing increasing disability.

    “Incomplete” is a relative phrase for those of us who are growing more incomplete by the day.

    • Jacques says:

      Doesn’t HSCT take care of the underlying problem of the body’s attack of myelin? Wouldn’t both be affective?

  3. spero says:

    What is not discussed are the numerous animal models that show that remyelination improves function. These conclusions are as premature as their claim that remyelination will have no effect.

  4. Darren says:

    Get the remylenation trials / studies carried out on humans and not rodents! I for one would volunteer. Any research regarding MS takes far too long; I WANT TO BE CURED. Would it help and speed up developments, not wishing this pathetic disease onto anybody, if the MS Consultants had MS? Not happy with the lack of urgency and I want my life as a functioning human being back. Thanks.

  5. Jamie Elder says:

    The only illness pharmaceutical companies make money on is cancer a cure would certainly affect their bottom line.perhaps research should go into finding the can’t find a cure before you know the cause.regardless ms is a cash cow for big pharma,one they don’t want to find a cure for.

    • Shasha says:

      HI, I agree. Most MS drugs are $5000 a month. They don’t want the next drug to be less than that. They are used to making money off MS people. Research money is abundant so many projects to use up the money. To me the answer is already here in Alternative medicine which helps remyelinate people and fix the root cause which maybe Celiac which causes low thyroid/heavy metals to build up/low Vit B12/low nutrients absorbed so cells are not made right in the brain/body to burn oxygen and the immune system is not working right.

      • Chris says:

        True research is only being done in small startup pharma companies. These researchers if you can even call them that, are just big corporation pharma talking. They are paid big money for these negative reports. Too bad this money was not used for real research.

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