A critical limitation of today’s stroke therapeutics is the narrow time window during which treatment can be administered safely and effectively. The vast majority of stroke victims aren’t even treated, leaving them with sensory, motor and cognitive disabilities. Clearly, a new approach to enhance functional recovery after a stroke is badly needed. For such a longer-term post-stroke recovery, a compound is expected to be administered within several days after the acute manifestation of stroke with continued treatment during the recovery phase.

A rodent model of neuronal plasticity was analyzed by gene expression profiling, using the imAGYne™ platform, to understand molecular mechanism and targets that could be used for pharmacological intervention after stroke to enhance functional recovery. In this model, animals are subjected to permanent middle cerebral artery occlusion (MCAO) model and are then placed in an enriched environment two days after MCAO. AGY found that animals placed in this environment recover significantly better than animals kept in a standard environment. Targets were identified from the gene expression analysis and compounds that mimic the benefits of the enriched environment by modulating these targets are currently under development.

AGY-208 is a neuronal receptor shown to be strongly up-regulated by the enriched environment. Agonists of this receptor provide strong neuroregenerative activity in vivo when administered the first time two days after permanent MCAO with continued daily treatment for 14 days. Improved function was assessed by a variety of sensory-motor and cognitive tests.

AGY has established a broad intellectual property position for the most valuable targets and lead compounds. In addition, the company established an intellectual property portfolio protecting its key technologies, including molecular cloning, bioinformatics for pathways, as well as the use of RNA interference (RNAi) in neurons and glial cells.
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