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Biotech / Medical : Incyte (INCY)
INCY 104.09-1.3%Nov 14 9:30 AM EST
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To: Biotech Jim who wrote (2841)3/18/2013 11:37:41 AM
From: Biotech Jim  Read Replies (1) of 3202
 
I have been asked to explain the potential relevance of the cns penetration of the small molecule ruxolitinib (Jakafi) in preclinical species (and by inference its brain penetration in man) and ptential mechanisms of the initiating event in JC virus activation. Further, how does this compare with the antibody natalizumab (Tysabri) in terms of the mechanism of JC virus activation in multiple sclerosis patients.

Wow, nice question.

A small molecule penetrating the CNS could block JAK 1 or JAK 2 in the CNS. Both enzymes are expressed in neurons in a variety of CNS neurons and pathways, but the functions related to viral activation or reactivation are not well studied. PML could result from CNS inhibition of these JAKs, but no data exists whatsoever for such biology as far as I look at the literature.

Tysabri is as we all know an antibody, that binds to an alpha4 integrin, a protein on several types of white cells (except for neutrophils) and blocks them from entering the CNS to attack their specific target as related to multiple sclerosis. Thus, they do not enter the CNS and allow for JC virus activation, the cause of PML.

So, totally different mechanisms operative in terms of potential adverse events (though the one case has NOT been established for ruxo).

(Need to correct a statement I made in an earlier post, I sold the last of my INCY trading shares last Thursday.)

I bet not too many folks in clinical at INCY are filling out their March Madness brackets today!
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