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 issue 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 novelneuroprotective 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 clinicaltrials.
Public Health Relevance Statement: Project Narrative (3 sentences) Traumatic brain injury (TBI) is a "silent epidemic" as 2.53 million patients visit the emergency department every year of which 56,800 patients die. Aruna Bio has recently developed a multimodal neuroprotective and regenerative neural stem cell extracellular vesicle (NSC EV) product, AB126â¢, to treat TBI that has demonstrated significant efficacy for TBI indications. The successful completion of the proposed 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.
Project Terms: porcine model, pig model, piglet model, swine model, Americas, Brain, Brain Nervous System, Encephalon, Cerebral hemisphere hemorrhage, Cerebral Brain Hemorrhage, Cerebral Hemorrhage, Cerebral Parenchymal Hemorrhage, Cerebrum Hemorrhage, Intracerebral Hemorrhage, Chemistry, Clinical Trials, Investigational Drugs, Investigational New Drugs, Edema, Dropsy, Hydrops, Epidemic, Future, Goals, Government Agencies, Grant, Health, Hemorrhage, Bleeding, blood loss, Hospitalization, Hospital Admission, Human, Modern Man, Industry, Inflammation, Laboratories, Magnetic Resonance Imaging, MR Imaging, MR Tomography, MRI, MRIs, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, NMR Imaging, NMR Tomography, Nuclear Magnetic Resonance Imaging, Zeugmatography, Methods, Mus, Mice, Mice Mammals, Murine, NIH, National Institutes of Health, United States National Institutes of Health, Patents, Legal patent, Patients, Pharmacology, Common Rat Strains, Rat, Rats Mammals, Rattus, Medical Rehabilitation, Rehabilitation, rehab therapy, rehabilitative, rehabilitative therapy, Rehabilitation therapy, Risk, Rodentia, Rodents Mammals, Rodent, Safety, Apoplexy, Brain Vascular Accident, Cerebral Stroke, Cerebrovascular Apoplexy, Cerebrovascular Stroke, brain attack, cerebral vascular accident, cerebrovascular accident, Stroke, Pigs, Suidae, Swine, porcine, suid, Family suidae, Testing, Tissues, Body Tissues, United States Food and Drug Administration, Food and Drug Administration, USFDA, Universities, nestin protein, nestin, Walking, nerve injury, neural injury, New Drug Approvals, Investigational New Drug Application, dosage, Area, Acute, Chronic, Clinical, Phase, Medical, Neurologic, Neurological, Evaluation, Lesion, Recovery, cerebral, Cerebrum, Funding, Dysfunction, Physiopathology, pathophysiology, Functional disorder, Therapeutic, angiogenesis, Attenuated, Supportive Therapy, Supportive care, Functional MRI, fMRI, Functional Magnetic Resonance Imaging, programs, Event, Emergency Department, Emergency room, Accident and Emergency department, experience, Toxicities, Toxic effect, novel, substantia alba, white matter, Modality, Position, Positioning Attribute, neurogenesis, Modeling, response, Brain Trauma, traumatic brain damage, Traumatic Brain Injury, Ischemic Stroke, nerve stem cell, Neural Stem Cell, neural precursor, neural precursor cell, neural progenitor, neural progenitor cells, neuron progenitors, neuronal progenitor, neuronal progenitor cells, neuronal stem cells, neuroprogenitor, FLK1, VEGF Receptors, VEGFR, VEGFR-2, VEGFR2, VPF Receptor, Vascular Endothelial Cell Growth Factor Receptor, Vascular Endothelial Growth Factor Receptor 2, Vascular Permeability Factor Receptor, KDR gene, Dose, Animal Testing, Data, Motor, Resolution, Rodent Model, Small Business Innovation Research Grant, SBIR, Small Business Innovation Research, Small Business Technology Transfer Research, STTR, Monitor, Therapeutic Effect, Development, developmental, preclinical study, pre-clinical study, controlled cortical impact, neuroinflammation, neuroinflammatory, efficacy evaluation, efficacy analysis, efficacy assessment, efficacy examination, evaluate efficacy, examine efficacy, functional outcomes, response to injury, injury response, Treatment Efficacy, intervention efficacy, therapeutic efficacy, therapy efficacy, Prevalence, aged, Impairment, clinically relevant, clinical relevance, commercialization, therapeutic development, therapeutic agent development, multimodality, multi-modality, neurological recovery, regenerative, animal efficacy, TBI treatment, TBI therapy, traumatic brain injury therapy, traumatic brain injury treatment, motor function recovery, recovered motor function, motor function improvement, improved motor function, Emergency department visit, ED visit, ER visit, Emergency care visit, Emergency hospital visit, Emergency room visit, Traumatic Brain Injury recovery, TBI recovery, recovery after TBI, recovery after traumatic brain injury, Assessment tool, Assessment instrument, extracellular vesicles, efficacy study, stroke model, neural network, side effect
