Categories  |  Inventors

Technology Overview

OHSU # 2944 — Small molecules promoting nerve regeneration

Summary

Nerve regeneration is critical after an injury for proper healing and restoration of function, but many tissues, such as the heart and spinal cord, lack this capacity due to extensive scarring resulting in more permanent injury and loss of function. Researchers at Oregon Health & Science have discovered novel compounds that promote nerve regeneration in tissues that normally undergoing scarring.

 

Technology Overview

Nerve damage is a major complication following myocardial infarction, traumatic brain injury, and spinal cord injury. The etiologies of these injuries are different, but the lack of nerve regeneration in each is due to production of chondroitin sulfate proteoglycans (CSPG) within scar tissue. Enzymatic degradation of CSPG enhances regeneration of peripheral nerves and spinal cord, but there are drawbacks to enzymatic treatment in humans, and no drugs are available to completely prevent CSPG inhibition of nerve regeneration. Protein tyrosine phosphatase receptor sigma (PTPσ), expressed on sympathetic nerves, is a major receptor for CSPG; therefore, novel compounds were designed to disrupt the PTPσ signaling pathway and tested for restoring axon growth in the presence of CSPG. The novel compounds increased axon outgrowth over culture plates containing CSPG in a dose dependent manner, with full restoration achieved at concentrations in the range of 100 nM.  In vivo testing 3 days following myocardial infarction in mice found that these compounds restored normal nerve density within the infarct, without signs of toxicity or widespread non-specific binding. In addition, these compounds were capable of reducing isoproterenol-induced arrhythmias post-infarction and also restored cardiac output to levels observed in sham uninjured mice. These compounds have demonstrated efficacy in vitro and in vivo to promote nerve regeneration through injury and CSPG expression, and could improve outcomes for a wide range of injuries that cause permanent nerve damage.

Publications

Sepe JJ, et al. “Therapeutics That Promote Sympathetic Reinnervation Modulate the Inflammatory Response After Myocardial Infarction.” JACC Basic Transl Sci. 2022 Aug 24;7(9):915-930. Link

Blake MR, et al. “Small Molecules Targeting PTPσ-Trk Interactions Promote Sympathetic Nerve Regeneration.” ACS Chem Neurosci. 2022 Mar 2;13(5):688-699. Link

Licensing

This technology is available for licensing and/or collaborative co-development.

 

Inventors:

Patents

Filed United States
Published United States WO 2022/051233 A1
Published United States US 2023/0373907 A1

Categories: