Combination treatment with tPA and IL2 analog for Stroke

Principal Investigator Program DirectorLastFirstMiddleChenRidong AbstractDue to its narrow time window of administrationup tohours post symptomsandfold increased risk of intracranial hemorrhagemerelyof acute ischemic stropke patients receive recombinant tissue plasminogen activatortPAthe only FDA approved drug for this indicationWhen tPA is given beyondhours of stroke onsetdeleterious effects of the drug ensueespeciallyhemorrhagic transformationHTwhich causes the most significant morbidity and mortality in stroke patientsIn animal modelstreatment with ILinduced regulatory T cells that improved stroke outcomes while attenuating HTRecent clinical trials have demonstrated that low doseof the cancer doseILtherapy was well tolerated and improved clinical outcomes in patients with autoimmune or inflammatory diseases without causing immunosuppression or increasing infectionClearlytreatment with low dose ILto induce regulatory T cells carries a high therapeutic potential to improve the efficacysafety and expand time window of tPA for stroke patientsCurrent ILtherapyAldesleukinkDis an unglycosylated recombinant ILfrom E coliRapid renal elimination results in a very short in vivo half life of ILin the range of minutes due to its small molecular sizeThis has been a major limitation for ILbased strategiesthus requiring the use of high and multiple doses of ILand causing toxic side effectsWe have designed and produced a novel ILbased therapyIn this studywe will follow the STAIR recommendations and RIGOR guidelines to conduct the Phase I preclinical validation of tPA and the proprietary ILanalog in male and female animals as innovative combination therapy for strokeSpecific AimDetermine whether combining tPA with the proprietary ILanalog will improve long term outcomes compared to the vehicle and tPA in the thrombo embolic stroke model of ratsh after occlusion Principal Investigator Program DirectorLastFirstMiddleChenRidong NarrativeThe proprietary ILanalog is a safe and powerful inducer of natural regulatory T cells that attenuates adverse immune responses associated with experimental strokeWe propose to determine whether the combination treatment with tPA will be safe and beneficial with at least ah therapeutic treatment window after stroke in a clinically relevant model of thrombo embolic stroke in rats