A research team at UTHealth Houston has received a $2 million grant from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health. The funding will support efforts to develop a new therapy for diabetic neuropathic pain that does not carry the risk of addiction associated with current treatments.
The project is part of the NIH HEAL Initiative, which aims to address chronic pain and opioid misuse in the United States. 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 are leading this effort. Their focus is on addressing the underlying causes of neuropathic pain rather than only managing symptoms.
Xin Alex Ge, PhD, professor of molecular medicine at McGovern Medical School, explained: “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.”
Diabetic neuropathic pain affects up to half of people with diabetes. It results from nerve damage due to prolonged high blood sugar levels but can also be caused by other factors such as pinched nerves or injuries.
Current therapies often rely on opioids or nonsteroidal anti-inflammatory drugs (NSAIDs), which have limited effectiveness and can lead to significant side effects including addiction.
Ge noted: “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. 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 studies identified matrix metalloproteinase-9 (MMP-9) as central in causing neuropathic pain. While small molecule inhibitors have been used in attempts to treat this condition, they often lack specificity and may interact with unintended targets.
The collaborative research group includes Ge; Ru-Rong Ji, PhD, professor at Duke University; Xinli Liu, PhD, associate professor at University of Houston; and support from the NIH HEAL initiative. They plan to create highly specific monoclonal antibodies targeting MMP-9 (anti-MMP9). Early clinical models suggest these antibodies could reduce mechanical and cold-induced pain while supporting nerve regeneration and mitochondrial health.
Over the next two years, researchers will focus on developing these antibodies and testing their effectiveness. By year five, they aim to start Phase I clinical trials involving human patients with diabetic neuropathic pain.
Kibaek Lee, PhD, postdoctoral fellow at McGovern Medical School, along with Sushma Krishnan, PhD, research scientist at McGovern Medical School will lead efforts in developing and optimizing anti-MMP9 antibodies.
Ge also holds an appointment at The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences.
This project is funded under award number 1UG3NS143650-01 from the National Institute of Neurological Disorders and Stroke.
