Small molecule modulators of PTP sigma for nerve regeneration

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Researchers at Oregon Health & Science discovered novel compounds that promote nerve regeneration in tissues that otherwise prevent neural growth due to scarring. Nerve injury is a major source of morbidity in the military whether from traumatic brain injury, spinal cord injury, or an extremity injury damaging peripheral nerves. The etiologies of these injuries are different, but the lack of regeneration in each is due to inhibitory extracellular matrix including chondroitin sulfate proteoglycans (CSPG). Regeneration of peripheral nerves and spinal cord is enhanced by enzymes that decrease CSPG. There are drawbacks to enzymatic treatment in humans, and no drugs are available to prevent CSPG inhibition of nerve regeneration. Protein tyrosine phosphatase receptor sigma (PTPs) is a major receptor for CSPG, and removing PTPs increases spinal cord regeneration. Novel compounds were designed to disrupt PTPs and tested for restoring axon growth on CSPG. One compound restored sympathetic growth at 1μM, without toxicity and preliminary data suggests it also restores growth of cerebellar neurons over CSPG. This is the first identification of a drug that can rescue neural growth over CPSG, and represents a significant advance to restore nerve growth in vivo.

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For Information, Contact:
Travis Cook
Senior Technology Development Manager
Oregon Health & Science University
Michael Cohen
Beth Habecker
Haihong Jin
Ryan Gardner
Matthew Blake
Therapeutics - Cardiology
Therapeutics - Neurology
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