Saturday, 30 April 2011

Mechanisms of fingolimod's efficacy and adverse effects in multiple sclerosis.

Cohen & Chun; Ann Neurol. 2011 May;69(5):759-77.

In addition to its immune effects Fingolimod readily penetrates the CNS and may have direct effects on neural cells. This central mechanism of action distinguishes Fingolimod from other immunosuppressive drugs and may explain its positive effects on reducing the rate of brain atrophy.

"Whether Fingolimod is neuroprotective is not a moot point; it's currently being tested in primary progressive MS. We will know the answer in approximately 3 years."

COI: I sit on the steering committee responsible for the phase 4 development of Fingolimod and our group has received grant support to assess Fingolimod in our secondary progressive animal model of MS.

12 comments:

  1. Prof G,

    Any thoughts on when neuro-protective agents might become available for MS patients e.g. SP patients? I think the CUPID study is reporting later this year. If the results are positive neuros need to be thinking of how to get patients on neuro-protective agents ASAP. Safety (for SP and PP patients) not such an important issue when brain atrophy is at stake i.e. we don't need years of further testing if agents look promising.

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  2. Prof G,

    I read a recent paper on B cells and cannaboids where you said that you believed that a treatment for progressive MS was just around the corner. What sort of timescale do you think it will be before such treatments are available?

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  3. You are correct that the CUPID study will be the first to report. However, as this is THC, the active ingredient in cannabis, it may have some regulatory and political hurdles to jump. I suspect a second confirmatory study will need to be done to get the drug licensed in the US. It is a pity the CUPID study was not done on top of an anti-inflammatory therapy; there is still a lot of inflammation in the brains and spinal cords of people with both SP and PPMS. Low dose THC is unlikely to do anything for inflammation.

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  4. You are correct in saying that people with SP & PP MS don't have time to hang around. This is one of the reasons that I am promoting a novel new phase 2 neuroprotective study design, which looks at the impact of drugs on the levels of neurofilaments in the spinal fluid of people with MS. This study will take ~12 months to do, unlike the CUPID study that will take ~6 years to report.

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  5. The most likely first real contender in relation to neuroprotection will be Fingolimod; the impact of Fingolimod on atrophy is very impressive and the drug targets inflammation.

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  6. Prof G,

    You say that SPMS and PPMS involve a lot of inflammation. Why don't the powerful anti-inflammatories such as Campath have any impact on the inflammation in these types of MS?

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  7. The comment on inflammation is based on the pathology of these disease subtypes and not the MRI studies. I think anti-inflammatory strategies are not sufficient as so much damage has already occurred that the damaged axons are nerves are primed for degeneration. The strategy I have been pushing is for a combination of an anti-inflammatory with a neuroprotective agent.

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  8. Would you consider fingolimod to be an immunosuppressant in the treatment of MS or would it be better described as a disease modifying therapy?

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  9. There is no doubt in my mind that Fingolimod is an immunosuppressant. However, it has other mechanisms of action that make if very interesting; i.e. potential neuroprotective and remyelination effects.

    All drugs that change the natural history of MS are called disease-modifying therapies. Several immunosuppressant drugs fall into this category.

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  10. Thanks for the reply. I now understand where my mental block was in this. So to clarify, fingolimod is an immunosuppressant and a disease modifying therapy, and interferons are immunomodulators and disease modifying therapy? I guess I'm just hung up on the classification of fingolimod vs. interferons.

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