According to a University of Notre Dame press release, the Accelerator Award is a $1.6 million research grant that will fund Chang’s project, “A Strategy to Accelerate Diabetic Wound Repair,” over the course of five years.
Chang’s project investigates the causes and molecular inhibitors of chronic wounds in diabetic patients. Chang said traditional treatments such as debridement remain ineffective for many diabetic patients.
“There are 73,000 amputations of lower limbs in diabetic patients in the U.S every year,” Chang said. “We’ve been trying to understand why the chronic wounds in diabetic patients do not heal.”
Chang said a key focus of the project is identifying and isolating MMP8 and MMP9 enzymes, also known as matrix metalloproteinase enzymes. She said one of these biological agents is critical to the healing process of diabetic wounds. Chang said a challenge the team will face is detecting and differentiating the three enzymes.
“It turns out that these enzymes are involved in the pathology and the effort of the body to heal the wounds ... The challenge is how to distinguish between the three enzymes. Current methods cannot differentiate between the three, and only one is involved in the pathology of the disease. ”
The team will also focus on activating and deactivating specific MMP8 and MMP9 enzymes, Chang said, since deactivating the MMP9 enzymes while leaving the MMP8 enzyme intact ensures faster recovery for chronic wounds. Chang said the project has primarily used mouse models (diabetic mice) to analyze the MMP8 and MMP9 proteins, but she hopes the project can take further steps to determine whether or not these proteins are found in human patients.
“Right now we have identified that an enzyme called MMP9 is involved in the pathology of the disease," Chang said. "We have identified that MMP8 is what the body uses to heal. Our strategy would be to inhibit the bad enzyme [MMP9] and leave the good enzyme [MMP8] untouched."
Chang said activating and deactivating the enzymes would be facilitated by a set of inhibitors her team has been able to identify. Chang said these inhibitors are “small molecular compounds that selectively inhibit the bad enzyme and do not inhibit MMP8.”
There is a lack of research and pharmaceutical interest in diabetic wounds, Chang said, despite the chronic health problems these present. She said she hopes her research will be able to translate to human trials.
“We do want to see our work translated into a therapeutic tool that will help patients with diabetic wounds," Chang said. "We want to analyze the [diabetic] tissue to see if we see the enzymes that are present in animals are present in humans. If we find them, this will give us more confidence that whatever will cure the wounds in mice will translate to humans."
