CMX-2043 Treatment Limits Neural Injury Pathophysiology and Promotes Neurological and Cognitive Recovery in a Pediatric Porcine Traumatic Brain Injury Model

Traumatic brain injury (TBI) represents a major global health issue contributing to significant disability and mortality. The TBI-induced secondary injury cascade, characterized by neuroinflammation, neural cell death, and tissue damage, results in lifelong functional deficits. Alpha-N-[(R)-1, 2-dithiolane-3-pentanoyl]l-glutamyl-l-alanine (CMX-2043) is a novel alpha lipoic acid (ALA)-based therapeutic that has neuroprotective, anti-apoptotic, and anti-inflammatory properties that mitigate cellular, tissue, and functional deficits following TBI. In this study, we evaluated the therapeutic efficacy of CMX-2043 on neural injury severity and functional recovery in a clinically relevant porcine TBI model.  MRI revealed that SQ and IV CMX-2043 administration reduced hemispheric swelling and atrophy, lesion volume, midline shift, and intracerebral hemorrhage and preserved diffusivity, cerebral blood flow, and white matter integrity. CMX-2043-mediated neuroprotection and regeneration were indicated by increased neural cell density, decreased neuroinflammation, and enhanced neurogenesis following SQ and IV administration. These cellular and tissue-level changes corresponded with reduced neurological deficits and rapid cognitive recovery as indicated by improved mRS and SRT results, respectively. Collectively, these results observed in a translational large animal porcine model suggest that CMX-2043 holds significant clinical value to potentially mitigate TBI pathophysiology and promote functional recovery. To read the full publication please click on the following link: https://pubmed.ncbi.nlm.nih.gov/40736023/