UTHealth Houston researchers awarded $2M to uncover a nonaddictive diabetic neuropathic pain therapy as the opioid crisis still looms in the US

UTHealth Houston researchers awarded $2M to uncover a nonaddictive diabetic neuropathic pain therapy as the opioid crisis still looms in the US

Written by: Sydney Lowther | Updated: September 19, 2025

A $2 million grant awarded to UTHealth Houston by the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, will allow researchers to develop a safe and effective way to treat diabetic neuropathic pain by inhibiting the key molecular target driving the discomfort.

In response to the NIH HEAL Initiative, researchers from the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases and the Department of Neurobiology and Anatomy at McGovern Medical School at UTHealth Houston will focus on the root cause of neuropathic pain rather than temporarily masking the symptom. Researchers hope to develop new therapeutics that will ultimately benefit those suffering from diabetic neuropathic pain.

"The pain drugs we have now are not very effective or safe, and can also be addictive. Our long-term goal is to develop a first-in-class, effective, and safe treatment for neuropathic pain that targets pain development and neuro-inflammation to stop pain where it began," said Xin Alex Ge, PhD, professor of molecular medicine and the Kay and Ben Fortson Distinguished Chair in Neurodegenerative Disease Research at McGovern Medical School.

Up to 50% of people with diabetes suffer from neuropathic pain. This pain stems from damaged nerve vessels caused when blood sugar levels are high for an extended period of time. It commonly affects people with long-term diabetes, like Type I and Type II, but the pain can also be caused by pinched nerves, inflammation, nutrient deficiencies, and injuries affecting the nerves.

The current treatment for neuropathic pain includes opioids and nonsteroidal anti-inflammatory drugs, but these common treatment options have limited effectiveness and considerable side effects, such as addiction.

"Matrix metalloproteinase-9 has been identified as a key factor for the pathogenesis of neuropathic pain, which makes it the perfect target for treatment therapies," Ge said. "Many people have applied this approach by developing inhibitors to block the function of a specific enzyme, but that poses a significant challenge that my team is working to overcome."

Previous research identified matrix metalloproteinase-9 (MMP-9) as the main enzyme that drives this pain and used small molecule inhibitors to treat it, but these methods lack specificity. Small molecules can often interact with multiple targets rather than the specified one.

The collaborative team, including Ge; Ru-Rong Ji, PhD, professor of anesthesiology at Duke University; Xinli Liu, PhD, associate professor of pharmaceutics at the University of Houston; and the NIH HEAL initiative, will develop highly specific monoclonal antibodies (anti-MMP9), advancing treatment methods from the status quo of symptom suppression to a new normal of disease management. Clinical models have shown that this method alleviates mechanical and cold pain, promotes nerve fiber regeneration, and enhances mitochondrial function.

In the first two years, the team will develop antibodies and test their potency and efficacy. By year five, the team hopes to begin the Phase I clinical trial on treating diabetic neuropathic pain in humans.

McGovern Medical School co-investigators Kibaek Lee, PhD, postdoctoral research fellow, and Sushma Krishnan, PhD, research scientist, will spearhead the development and optimization of anti-MMP9 antibodies.

Ge is also a faculty member at The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences.

This project is supported by the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, under award number 1UG3NS143650-01.