Drugs take time to Work

Yokoseki A, Saji E, Arakawa M, Hokari M, Ishiguro T, Yanagimura F, Ishihara T, Okamoto K, Nishizawa M, Kawachi I. Relapse of multiple sclerosis in a patient retaining CCR7-expressing T cells in CSF under fingolimod therapy. Mult Scler. 2013 Mar 21. [Epub ahead of print]

Fingolimod acts as a functional antagonist of the sphingosine-1-phosphate receptor, and it traps lymphocytes in secondary lymphoid organs (lymph glands) and precludes their migration into the central nervous system. We report the case of a patient who suffered a relatively severe relapse of multiple sclerosis(MS) during the initial 3 months of fingolimod therapy, with retention of CCR7 expression on CD4+ T cells in the cerebrospinal fluid (CSF) despite decreased numbers of lymphocytes and decreased expression of CCR7 on CD4+ T cells in the blood. These data suggest that fingolimod may cause differential effects on the CSF and blood lymphocytes of patients with MS during the initial months of therapy.

In many studies of drug treatment with potent immunosuppressive agents there may be relapses within the first few, about 3, months of treatment. This suggests that the relapse was going to happen and the administration of drug was too late to stop it. This study is therefore interesting as it suggests that cells that may be disease forming have been recruited into the brain, ready to do their worst. Whilst fingolimod (Gilenya) was given and emptied the blood it was too late to deal with the immune response in the brain and there were immune cells in the cerebrospinal fluid. This is worth bearing in mind when in trials or following treatment that it make take some time for the treatment to become effective. So if you have a relapse shortly after starting drug treatment it does not mean that they are ineffective . Gilenya can get into the brain, but if its action is in the lymph glands then this action is feature has little relevance for this aspect of disease.

Now look at the data from ORACLE data and cladribine yesterday, If the the people getting disease in the first 3 months are removed from the equation (i.e. about 5%) then maybe 10 pills could have stopped 75% of people developing MS…..2 years after their first sign……could they be cured?

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  • Does this delay then apply to all the DMDs that affect the peripheral immune system rather than working inside the brain? Is that all of the existing DMDs? How long do you think it would take for BG12 to become effective after someone started taking it since no one seems to know exactly how it works?

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