Thursday, 26 September 2013

Cladribine works in rodents Should it?

Musella A, Mandolesi G, Gentile A, Rossi S, Studer V, Motta C, Sepman H, Fresegna D, Haji N, Paolillo A, Matarese G, Centonze D. Cladribine interferes with IL-1β synaptic effects in experimental multiple sclerosis. J Neuroimmunol. 2013 Aug. doi:pii: S0165-5728(13)00230-0. 10.1016/j.jneuroim.2013.08.009. [Epub ahead of print]
Alterations of glutamate-mediated synaptic transmission occur in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the animal model of MS. Here we investigated whether intracerebroventricular (icv) administration of cladribine has effects on EAE. Icv infusion of cladribine reduced the clinical deficits of EAE mice and reversed EAE-induced enhancement of excitatory postsynaptic current (sEPSC) frequency, a neurophysiological measure of glutamatergic synaptopathy associated with central inflammation. Cladribine failed to interfere with EAE-induced microglial and astroglial activation, but blocked EAE synaptic alterations by interfering with interleukin-1β effects. Cladribine possesses neuroprotective properties in experimental MS that are independent of its peripheral immunosuppressant action.

This study says cladribine has beneficial activities independent of immunosuppressant action. However does it matter? 



Cladribine is the drug that has been thrown down the toilet by pharma, 



This is sad when you think why.......it is probably as least as effective as any other DMT  and probably safer than many.... if only the placebo group had behaved normally in the trial, Lemtrada would be having a run for its money...Generic version is available...at a fraction of the cost. 

However big question is does cladribine work really work in rodents,? Aren't their immune cells resistant to the effects of Cladribine, in contrast to the effects in humans? Anyone for Merck care to comment as they sponsored the study. 

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