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Thread: New perspectives on multiple sclerosis

  1. #1 New perspectives on multiple sclerosis 
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    Know someone with multiple sclerosis?

    This is latest info on MS from Nat Rev Drug Discov. 2008 Nov;7(11):909-25 reviewed here:
    The overall perspective has shifted to MS being a constitutive diffuse syndrome rather than the classical notion of a multifocal disease with periodic heightened immune activation.
    The traditional understanding is challenged by mounting evidence and has lead to the hypothesis that the dysregulation of the innate immune system may be a key factor in the shift toward irreversible neurodegeneration and MS progression. This hypothesis implies that components of the immune system previously thought to be uninvolved may be contributing to disease progression. These include dendritic cells, natural killer T cells, and resident microglia. This newly realized complexity of MS progression explains the previously limited ability to provide accurate prognosis for a significant number of patients, as well as the limited efficacy of FDA approved therapies.


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    Forum Cosmic Wizard i_feel_tiredsleepy's Avatar
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    I've actually been attending a series of guest lectures on MS here at McGill this week.

    The current approved drugs (there are 2 of them both T cell inhibitors I believe, can't remember since I'm a terrible immunologist) require near daily injections and are only like 30-50% effective. Relatively safe though. (edit: Ones interferon I can't remember what the other one is)

    The new drugs that are currently in Phase 3 trials, like fingolimod, are quite interesting. Fingolimod is an inhibitor of a receptor involved in the localization of immune cells, inhibiting this receptor results in sequestering naive T-Cells in the lymph nodes. As an immunosuppressant this has amazing possibilities, it will inhibit new immune responses while memory cells in the periphery will still be able to effectively fight infections that the individual has encountered before. So, this drug is more promising for uses in transplant patients, but it has shown a 80% efficacy in reducing MS symptoms. In one trial though 7 of 30,000 people developed PML, a viral infection that is usually only seen in advanced AIDS patients. So, it comes with risks, but it can be given as a pill making it much more convenient as well as effective for MS patients.

    There is research being done on drugs that target B cells and such going on, as well as research into identifying the antigens responsible for the autoimmunity, these could potentially be useful in the future.

    Finally, currently a trial is going on in Ottawa with complete immune ablation and bone marrow transplants to cure MS. So far the patients who survive the procedure have not had any relapses, a very dangerous procedure but a potential cure.

    Sadly we still don't have any effective treatments to slow progressive stage MS as of yet. Thus, early diagnosis remains vital for effective treatment.


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    Thanks for the insights.

    Fingolimod does seem promising. I didn't know about the 7/30,000 patients developing PML. I wonder if PML causing viral infection would go away if the patient gets off of fingolimod.

    The latitude correlations of MS occurrence and possible role of vitamin D3 are intriguing. Do you know if lifestyle modifications are recommended for patients in early stages of MS?
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  5. #4  
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    No the PML is caused by Tysabri (natalizumab) but as far as I know most cases were when patients were coadministered beta interferon so that is now a contraindication.

    There isnt really much lifestyle influence on the disease but physiotherapy can reduce the disbaility from attacks.
    Havent heard about vitaminD?
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  6. #5  
    Forum Cosmic Wizard i_feel_tiredsleepy's Avatar
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    Quote Originally Posted by Robbie
    No the PML is caused by Tysabri (natalizumab) but as far as I know most cases were when patients were coadministered beta interferon so that is now a contraindication.

    There isnt really much lifestyle influence on the disease but physiotherapy can reduce the disbaility from attacks.
    Havent heard about vitaminD?
    You're right the fingolimod was the one where the school teacher died of chicken pox because she had never gotten it before. (Sorry, got the drugs mixed up in my head).

    I think the Vitamin D stuff comes from the correlation of higher rates of MS in the northern hemisphere, however I think this might have more to do with some unforeseen correlative because there are huge differences in lifestyle between the predominantly richer northern nations and the countries near the equator. As far as I know no one has ever proposed any logical reason why lower Vit. D would cause MS.

    Edit: Either way both Tysabri and Fingolimod are very promising drugs for MS patients.

    Edit2: Should always double check what I say, the danger of posting from memory
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    This is from Wikipedia..I don't completly trust using it as a resource but this information seems to coincide with what I've read in the past on the subject:


    Interferon beta-1a is a drug in the interferon family used to treat multiple sclerosis (MS).[1] It is produced by mammalian cells while Interferon beta-1b is produced in modified E. coli. Interferons have been shown to have about a 18-38% reduction in the rate of MS relapses, and to slow the progression of disability in MS patients [2]. None of the products on the market is a cure, but patients today who start early on Interferons may beneficially alter the natural course of the disease.

    There are two principal competitors in the market for this drug and one biogeneric / biosimilar one:

    Avonex (Biogen Idec)
    Rebif (EMD Serono)
    CinnoVex (CinnaGen)


    It is believed that Interferon beta based drugs achieve their beneficial effect on MS progression via their anti-inflammatory properties. Studies have also determined that Interferon beta improves the integrity of the blood-brain barrier (BBB), which generally breaks down in MS patients, allowing increasing amounts of undesirable substances to reach the brain. This strengthening of the BBB may be a contributing factor to Interferon-Beta's beneficial effects. These studies were carried out in vitro (outside a living organism; a "petri dish" experiment), so it does not necessarily mean it works the same in people.

    Nonetheless, Interferons have side effects. The two main ones are flu-like symptoms, and injection-site reactions. The flu-like symptoms tend to happen immediately after the injection, and last for about half a day.[citation needed] In many patients, these symptoms diminish over time, but some patients continue to experience them over the long term. One can mitigate these symptoms by using a dose that is injected less frequently, and by taking the medication before bedtime. The injection-site reactions can be mitigated by rotating injection sites, or by using one of the medications that requires less frequent injections. Side effects are often onerous enough that many patients ultimately discontinue taking Interferons (or glatiramer acetate, a comparable disease-modifying therapies requiring regular injections).

    The most commonly reported side effects are injection site disorders, flu-like symptoms, poor results on liver function tests and blood cell abnormalities. More serious side effects include depression, seizures or liver problems.

    While these drugs improve certain diagnostic test results they do not cure MS and many patients report no perceived improvement but serious side-effects that substantially reduce quality of life. Over time, physiological tolerance and reduced effectiveness can occur due to the development of antibodies to the drugs and side effects may persist even after discontinuation.
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