Treatment of stroke using a novel PDZ binding peptidomimetic drug.

DESCRIPTION (provided by applicant): Abstract Stroke is the third leading pathological cause of death, behind heart and cancer (NCHS mortality data.). We are developing a new drug, CN 2097, that has demonstrated therapeutic potential for stroke. CN 2097 obstructs the propagation of the cell death signal whilst not interfering with normal neuronal transmission, thus reducing the incidence of side effects and toxicity but allowing the titration of a therapeutic dose. This Phase I SBIR study will involve confirming the therapeutic potential of this drug by confirming its favorable pharmacokinetic profile and proving efficacy in the middle cerebral artery occlusion (MCAo) model. The first milestone will be producing sufficient additional quantities (500mg) of CN2097 to complete the pre-clinical in-vivo studies proposed in Aim 2. The second milestone will be the demonstration that CN 2097 has sufficient bioavailability and stability to cross the blood brain barrier and prevent MCAo-induced ischemic stroke neuronal damage and the significant decrease of disabling injury. Based upon our previous results we anticipate that CN 2097 will be an effective treatment in the MCAo model of stroke and will attain therapeutic brain concentrations. Completion of these reliable animal model studies will allow us to enter Phase II development of CN 2097, focusing on toxicology and dosage form design in preparation for Clinical trials. SBIR provides a bridge that will translate our laboratory studies into a Clinical treatment for stroke. PUBLIC HEALTH RELEVANCE: Narrative This project is designed to undertake pre-clinical trials that will provide compelling evidence that this innovative drug, CN 2097, has the potential to prevent or treat the damage caused by stroke. Stroke is simultaneously one of the deadliest diseases and also one of the most undertreated; the emergence of this drug as a viable treatment will eliminate stroke as a major threat to humans. This will result in a drastically changed public health climate, resulting in less disability and longer, more productive life spans amongst the victims of stroke.