A team of UTHealth Houston researchers slowed and even reversed diabetic nerve damage in mice, bringing researchers one step closer to developing a treatment for humans.
The research was published today in Science Translational Medicine .
Diabetic peripheral neuropathy describes nerve damage in the hands, legs, and feet caused by diabetes. Over time, high levels of blood sugar can injure nerve fibers, with symptoms ranging from numbness, a tingling or burning sensation, muscle weakness, to pain and cramps.
Up to half of the more than 40 million diabetic individuals in the United States will develop peripheral neuropathy, making it the most common chronic complication of diabetes.
“There is no good drug for managing peripheral neuropathy,” said corresponding author Xin (Alex) Ge , PhD, professor in the Texas Therapeutics Institute at The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases within McGovern Medical School at UTHealth Houston. “There are painkillers and other drugs, but they are only targeting the symptoms.”
To cure the condition in mice with Type I and Type II diabetes, the team focused on an enzyme known as matrix metalloproteinase-9, or MMP-9. This enzyme can break down other proteins found between tissues. It is responsible for excess immune response in the peripheral nervous system and disease progression that impaires wound healing.
Ge and the team developed monoclonal antibodies, a type of treatment that blocks matrix metalloproteinase-9 activity in a highly specific manner.
“Developing an antibody that selectively targets MMP-9 has been challenging because MMP-9 is closely related to other enzymes. To overcome this challenge, we combined a camelid-inspired antibody library design with a functional selection approach to identify antibodies that specifically inhibit MMP-9,” said first author Kibaek Lee, PhD, a postdoctoral research fellow at the Institute of Molecular Medicine. “These new biotechnologies separate our antibodies from others.”
Mice injected with the antibodies regenerated nerve fiber and showed improved wound healing in their paws.
“ This gives us hope that we can not only relieve the symptom, but also reverse the progression of disease,” said Ge, who holds the Kay and Ben Fortson Distinguished Chair in Neurodegenerative Disease Research at McGovern Medical School.
This work is partially supported by the NIH HEAL Initiative, a project with the goal of developing safe, effective, and nonaddictive pain medications.
Sushma Krishnan, PhD, a research scientist at the Institute of Molecular Medicine, was a co-author on the paper.
Authors from Duke University Medical Center include Wei He, PhD; Yutaka Matsuoka, PhD; Sangsu Bang, PhD; Jing Xu, PhD; Qin Zhang, MD; and Ru-Rong Ji, PhD.
Additional authors include Xinli Liu, PhD; Letao Ma, MS; and Weiyuan Hu, MS, of the University of Houston, and Luda Diatchenko, MD, PhD; Xiang Ao, PhD; and Marc Parisien, PhD, of McGill University.
Science Translational Medicine
Monoclonal antibodies inhibiting MMP-9 activity alleviate peripheral neuropathy in diabetic mice
9-Sep-2026