Project Grant R41NS122704

NEURAL STEM CELL EXTRACELLULAR VESICLE TREATMENT FOR TRAUMATIC BRAIN INJURY - PROJECT SUMMARY/ABSTRACT TRAUMATIC BRAIN INJURY (TBI) IS A UNIVERSAL HEALTH CONCERN AND IS KNOWN AS A "SILENT EPIDEMIC". EACH YEAR IN AMERICA, 2.53 MILLION PATIENTS VISIT THE EMERGENCY DEPARTMENT AFTER SUFFERING A TBI OF WHICH 56,800 DIE AND OVER 288,000 REQUIRE HOSPITALIZATION, REHABILITATION PROGRAMS, AND LONG-TERM SUPPORTIVE CARE. ALTHOUGH THE PRIMARY TBI EVENT IS TYPICALLY ACUTE, SUBSEQUENT SECONDARY INJURY RESPONSES (NEUROINFLAMMATION) AND CHRONIC TISSUE LOSS OFTEN RESULT IN FUNCTIONAL DEFICITS THAT LAST A LIFETIME. PRESENTLY, THERE ARE NO NEUROPROTECTIVE OR REGENERATIVE FOOD AND DRUG ADMINISTRATION APPROVED TBI TREATMENTS. ARUNA BIO HAS RECENTLY DEVELOPED A NOVEL NEUROPROTECTIVE AND REGENERATIVE NEURAL STEM CELL EXTRACELLULAR VESICLE (NSC EV) PRODUCT CALLED AB126 THAT MAY BE USED TO TREAT TBI. AB126 HAS DEMONSTRATED MULTIMODAL THERAPEUTIC EFFICACY IN DIVERGENT SPECIES (AGED MOUSE, RAT, PIG) AND NEURAL INJURY MODELS (TBI, STROKE). IN TBI RODENT MODELS, AB126 REDUCED LESION SIZES, ENHANCED ENDOGENOUS NEUROGENESIS AND ANGIOGENESIS, AND RAPIDLY ATTENUATED MOTOR FUNCTION IMPAIRMENTS. LARGE ANIMAL TESTING HAS BEEN REPEATEDLY IDENTIFIED BY ACADEMIC, INDUSTRY, AND GOVERNMENT AGENCIES AS A KEY DE-RISKING STEP IN TBI THERAPEUTIC DEVELOPMENT. TO THIS END, THIS PROPOSAL OUTLINES FDA ENABLING STUDIES IN A PIG CONTROLLED CORTICAL IMPACT TBI MODEL USING CLINICALLY RELEVANT ASSESSMENT TOOLS TO EVALUATE THE EFFICACY AND SAFETY OF AB126 AS A TREATMENT FOR TBI. THE SUCCESSFUL COMPLETION OF THIS STUDY WILL PROVIDE KEY INFORMATION PERTAINING TO AB126 DOSAGE, THERAPEUTIC EFFECTS ON TBI PATHOPHYSIOLOGY (EDEMA, HEMORRHAGE) AND FUNCTIONAL OUTCOMES, TOXICITY, AND POTENTIAL ADVERSE SIDE EFFECTS THAT WILL SERVE AS THE BASIS FOR AN IND SUBMISSION AND FUTURE CLINICAL TRIALS.