New Drug Has Potential to Protect Brain Cells from Traumatic Injuries

February 1, 2019 • by Marc Airhart

Stephen Martin and James Sahn have demonstrated that a new compound protects brain cells in mice that have been subjected to brain trauma, raising the prospects of a possible treatment for humans who experience TBI.

Illustration of the interior of the brain showing active neurons lit up

Traumatic brain injuries (TBIs), caused by everything from falls to being hit by moving objects to car crashes, cause nearly a third of all injury-related deaths in the U.S. Millions of survivors struggle with impaired thinking and movement, personality changes or depression.

A team of chemists from The University of Texas at Austin led by Stephen Martin and James Sahn, has demonstrated that a new compound protects brain cells in mice that have been subjected to brain trauma, raising the prospects of a possible treatment for humans who experience TBI. They reported their results in November in the journal ACS Chemical Neuroscience.

The researchers tested a novel compound called DKR-1677 that binds to a nerve cell receptor shared by mice and humans called the sigma 2 receptor (sigma2R) or transmembrane protein 97 (TMEM97). When treated with DRK-1677 after a TBI, mice had less damage to neurons and other cells in the brain than untreated mice. Treated mice were also better able to perform a cognitive task called the Morris water maze. This is the first time anyone has shown that compounds that bind to this receptor are efficacious in animal models of TBI.

The receptor sigma2R/TMEM97 is emerging as an attractive biological target for treating a number of neurological conditions. For example, it has been previously implicated in several neurological disorders including Alzheimer's disease and schizophrenia. In addition to their recent work with TBI, Martin, Sahn and their collaborators have also shown that other compounds that bind to this receptor have beneficial effects in other animal models, including alcohol use disorder and neuropathic pain.

Martin and Sahn have co-founded NuvoNuro, an Austin-based drug company with a focus on developing effective therapies to treat neurodegenerative and neurological disorders. NuvoNuro's proprietary technology is based on modulation of sigma2R/TMEM97. Martin, Sahn and the NuvoNuro team plan to advance some of their compounds towards human clinical trials.

The University of Texas at Austin is committed to transparency and disclosure of all potential conflicts of interest. University investigators involved in this research have submitted required financial disclosure forms with the university. Martin and Sahn have equity ownership of biotech startup NuvoNuro.

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