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NOVEL APPROACHES TO TRAUMATIC BRAIN AND SPINAL CORD INJURIES • Traumatic brain and spinal cord injuries (TBI & SCI) are incurred by over 1.7M individuals yearly in the US alone • There are currently no effective treatments for TBI and SCI resulting in significant unmet need • Recovery from these central nervous system (CNS) injuries is poor due to the limited capacity of the neurons to regenerate • Scientists at the University of Helsinki have discovered two molecules, UH0113 and UH0213 (both peptides/proteins) that promote neuronal regeneration and growth in the injured brain and spinal cord, thus representing novel strategies for CNS injuries CSPG + UH0113 Functional testing, SCI Control UH0113 Number of axons B Control UH0113 Days post injury In vivo imaging, TBI C 50 40 30 ctrl (UH0113) ctrl (UH0213) UH0113 sham UH0213 20 p=0.03 E 10 baseline 1,6 2 4 6 8 10 D ctrl UH0113 1,2 UH0213 0,8 Vessel length, normalized Number of axons A Time to climb up, s In vivo imaging, SCI CSPG + UH0213 Dendrite density, normalized CSPG + IgG Average score, pts CSPG UH0113 and UH0213 promote neurite outgrowth. Chondroitin sulphate proteoglycans (CSPGs, immobilized on the substrate) inhibit axonal growth in embryonic rat cortical neurons in vitro. UH0113 and UH0213 overcome this inhibitory action. p=0.05 F 0,4 1 3 5 7 9 20 days post injury Weeks post injury UH0113 and -0213 restore neuronal growth and functions after injury. UH0113 increases the number of axons within (A) and crossing over (B) an injury site. Following SCI, UH0113 and -0213 enhance locomotor activity as measured by vertical grid climbing (C) and trauma assessment test (D). Following TBI, UH0113 enhances dendrite density (E) and blood vessel length (F). In the SCI model, following injury (laminectomy of two vertebra and transection of dorsal sensory tracts on one side of the spinal cord) UH0113 or -0213 was injected to the injury site in adult mice, UH0113 on day 0 and -0213 on day 3 post injury. In the TBI model, following injury (needle prick to the parietal lobe of the brain cortex), UH0113 was injected to the injury site in adult transgenic mice expressing YFP in dendrites, and chronic cranial window was used to follow dendrite regeneration using two photon microscopy on live animals over 20 days. Sham-operated mice did not receive any treatment. Intellectual property & offer • PCT applications, relating to the use of UH0113 and UH0213 for treating TBI, SCI and other neuronal injuries have been filed. • We are currently seeking investment and co-development opportunities for this technology. Contact Dr Kirsty Hewitson Director, Life Sciences Helsinki Innovation Services [email protected] Tel: +350 50 572 2281 www.his.fi