Many diabetic patients suffer associated complications with their disease, but Dr. Mayland Chang, a research professor in the department of chemistry and biochemistry, is attempting to mitigate the complication of chronic wounds.
“Diabetes has many complications and one of them is that patients with diabetes get wounds that don’t heal,” Chang said.
She said there is almost no knowledge of the causes of this specific complication, and this limited knowledge has led to the inability to combat the problem.
“This results is more than 70,000 lower limb amputations in patients every year just in the U.S.,” she said. “About half of those patients, within three years, end up dying.”
These statistics drove Chang to look for solutions to these problems, she said. Chang leads a research group from Notre Dame’s department of chemistry and biochemistry that has made significant progress in finding ways to fix the prevalence of chronic wounds in diabetic patients.
The team’s main tools are diabetic mice, she said.
“We inflict wounds to mice, db/db mice, so they have type 2 diabetes, and we go with a biopsy punch,” Chang said. “If you can imagine it, it is like trying to punch a hole in paper, you make a wound in the back of the mice.”
The research team is able to analyze the mice wounds and gather data, she said, and the mice have already led the team to new discoveries. In an earlier study, the research team found two enzymes in the diabetic mice wounds: MMP-8 and MMP-9.
Chang said the research team hypothesized that MMP-8 was coming in to repair the wound.
“We also saw that MMP-9 up regulated in diabetic animal wounds, so we thought that MMP-9 was the cause for why the wounds did not heal,” she said.
The first study also led to the team to utilize an MMP-9 inhibitor, ND-322, in attempt to heal the wounds, Chang said, but the results did not overly impress the team.
“We would see improvement, but not great improvement, so then we worked on making a more selective inhibitor,” she said.
In their most recent study, published in the Proceedings of the National Academy of Sciences, the team utilized a new and improved MMP-9 inhibitor, ND-336, Chang said. While low levels of selectivity lessened the earlier inhibitor’s healing abilities, the new inhibitor, ND-336, is far more sophisticated, Chang said..
“The ND-322 was a three-fold selectivity, this is like a 50-fold selectivity,” she said.
Chang said ND-336 is a much better inhibitor, and now that the team has proven their discoveries yield successful results, she can envision the practical benefits of these discoveries.
“If you had an MMP-9 inhibitor like ND-336, that in itself can become a drug that you can apply to heal wounds,” Chang said.
Other options, Chang said, would be to apply MMP-8 to the wounds or utilize the combination of both. First the team would have to move on to human trials, she said, which will not be happening in the near future.
“You need first to get investment money that usually does not come from federal agencies. It may be like $2 million to manufacture kilograms of the compound that we can’t do here, and then be able to do the toxicology in a rodent and non-rodent species. We would submit that to the FDA and then they would grant us approval so we can test on humans,” Chang said.
Finances, not time, are the main obstacle, Chang said.
“It is not that it is a long road, it is that you have to go and find the money to do it. If you have the money, you can get it done in one year. The problem is just getting the money to do that,” she said.
