Therapeutics Targeting Nogo-A Hold Promise for Stroke Restoration

Prateek      Kumar; Lawrence D.F.      Moon

Abstract

Neurorestorative therapies for stroke aim to reverse disability by reparative mechanisms (rather than to thrombolyse or to neuroprotect). A substantial and persuasive body of pre-clinical evidence has come from the evaluation of antibodies against Nogo-A (a myelin-associated inhibitor of plasticity) in rat models of stroke. Particularly impressive is the benefit of this therapy in models of permanent middle cerebral artery occlusion (MCAO) when given to elderly animals after a one week delay, in adult rats with co-morbidities, and in adult rats when treatment is delayed by up to 9 weeks after stroke (although antibodies against Nogo-A did not reverse disability in mice after proximal MCAO with reperfusion). We predict that antibodies against Nogo-A will improve outcome further when combined with suitable additional rehabilitation, and also that antibodies against Nogo-A will improve outcome in animal models of haemmorhagic stroke that affect the same brain regions as ischemic stroke caused by MCAO. Antibodies against Nogo-A have been shown to be safe in Phase I clinical trials for acute spinal cord injury, and this may eventually facilitate a trial in stroke.

Keywords: Neurorestoration, stroke, cerebral ischemia, Nogo, antibodies, plasticity.

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