Selection & Optimization of a Therapeutic Protein for Acute Ischemic Stroke Functional Recovery

Project Summary Abstract Stroke is a leading cause of serious long term disabilityAnnual incidence is approximatelyin the USandworldwideOnlyof stroke survivors return to full normal function and activityOvermillion people in the US have survived a strokebut continue to live with its debilitating effectsEighty seven percentof strokes are ischemicdamage resulting from lack of blood supply to a particular region of the brainIt is estimated that approximately fifty percent of ischemic strokes results from Emergent Large Vessel OcclusionsELVOswith an acute blockage of a main artery in the brainThis subgroup of stroke is particularly attractive as an initial target for therapeutic clinical trialsas the patient population and disease presentation is more homogenousthe current therapeutic paradigm is well establishedand the potential for benefit is greatest as ELVO causes the most severe and disabling type of strokeStream Biomedical is commercializing a therapeutic proteinrecombinant human perlecan domain VrDVwhich has been shown in small animals to be significantly neuroprotective and neuroreparativeangiogenic and neurogenicresulting in dramatic functional improvement when administered acutely after ischemic strokeThe initial target therapeutic indication is for the treatment of acute ischemic stroke resulting from ELVOand the clinical objective is to improve functional outcomes post strokeThe development objectives of this translational proposal are to conduct studies to determine a preference for rDV or its fragment rLGas the therapeutic candidateto develop and define a preferred scalable recombinant microbial production process and conduct IND enabling studies of the lead protein process candidate including protein characterizationdose range findingpharmacodynamicssafety pharmacology and toxicology Project Narrative There is currently no product on the market for functional stroke recovery that is neuroprotectiveangiogenic or neurogenicDV will serve a great unmet needThe need will continue to grow as the elderly proportion of populations in the US and all developed countries is projected to increase by overbetweenandOnce proven to be as effective in humans as has been demonstrated to date in experimental animalsour therapy will restore the productivity and quality of life for millions of individuals and will significantly reduce the burden on families and on society in general