Lesional-targeting of neuroprotection to the inflammatory penumbra in experimental multiple sclerosis



Studies have shown that progressive MS is associated with metabolic failure of axons and excitotoxicity which leads to neurodegeneration. The global blockade of sodium channels can cause side-effects that restrict its use for neuroprotection in MS.

This study looked at the selective targeting of drugs to lesions to help improve the therapeutic window in relapsing-progressive experimental autoimmune encephalomyelitis (EAE) model of MS using conventional sodium channel blockers and a new CNS-excluded sodium channel blocker (CFM6104). CFM6104 selectively targets the inflammatory area in EAE lesions. CFM6104 was >90% excluded from the CNS in normal mice;  however, it entered the CNS during the inflammatory phase in EAE.. This tended to occur after the focal and selective down-regulation of endothelial p-glycoprotein at the BBB in both EAE and MS. They found that CFM6104 significantly slowed down the accumulation of disability and nerve loss in EAE.

By targeting drugs to lesions, this may reduce the potential side-effect profile of neuroprotective agents that can influence neurotransmission. By targeting this class of agent, it results in inhibition of microglial activity and neural sodium loading, which are both thought to contribute to progressive neurodegeneration in MS.

Authors: Al-Izki S, Pryce G
Source: Brain. 2013 Nov 27. [Epub ahead of print]
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