Researchers land funding to help launch diabetic ulcer drug over ‘Valley of Death’ | News | Notre Dame News | University of Notre Dame Skip To Content Skip To Navigation Skip To Search University of Notre Dame Notre Dame News Experts ND in the News Subscribe About Us Home Contact Search Menu Home › News › Researchers land funding to help launch diabetic ulcer drug over ‘Valley of Death’ Researchers land funding to help launch diabetic ulcer drug over ‘Valley of Death’ Published: October 07, 2019 Author: Deanna Csomo McCool Mayland Chang and Shahriar Mobashery in their office in McCourtney Hall. Photo by Matt Cashore/University of Notre Dame. Thousands of new chemical structures are tested in hopes of discovering a single drug meant to treat a single disease. Of the 5,000 to 10,000 that are prepared, only about 250 of those make it to the pre-clinical stage, and potentially as few as five make it to clinical trials in humans. The gap between discovery and clinical research is dubbed the Valley of Death — the place where promising compounds languish because of lack of funding in academic labs and start-up companies. But one compound developed at the University of Notre Dame recently received funding from the Department of Defense for this pre-clinical phase, allowing the drug to move beyond discovery and toward clinical trials in humans. The compound, called (R)-ND-336, is a topical gel for treatment of diabetic foot ulcers. It was developed by Mayland Chang, research professor in the Department of Chemistry and Biochemistry, and Shahriar Mobashery, the Navari Family Professor in Life Sciences in the Department of Chemistry and Biochemistry. Both are affiliated with Advanced Diagnostics & Therapeutics and the Warren Family Research Center for Drug Discovery and Development. About 25 percent of all patients with diabetes will develop foot ulcers. Elevated blood glucose causes numbness in the extremities, and the patients cannot feel the ulcers forming. They are notoriously difficult to heal. The $4.6 million award from the Department of Defense will help fund the expensive studies required before the compound can be given approval by the FDA to be tested on people. Chang and Mobashery expect this pre-clinical phase to last two years, and both anticipate the compound to move ahead to human trials. Additionally, they have shown that it should not cause cancer or have other toxic side effects. “Many times what happens is some drugs go into the market and pharmaceutical companies may just know that it works in humans, but they don’t really know how,” Chang said. “But we took a very systematic approach to address these issues.” They evaluated the effectiveness of becaplermin, the only FDA-approved drug on the market to treat diabetic ulcers, which was introduced 20 years ago. It uses a growth factor to stimulate tissue healing and is moderately effective, but comes with a black box warning for an increase in cancer and death. They compared its effectiveness with (R)-ND-336 in diabetic mice, and showed that (R)-ND-336 was more effective. Chang and Mobashery looked at the specific enzymes, called matrix metalloproteinases (MMPs), involved in remodeling tissues, and discovered that two closely related MMPs played roles in diabetic wound healing. One of the enzymes, MMP-9, slows healing, while the other one, MMP-8, promotes it. Therefore, broad-spectrum drugs that inhibit both of these MMPs would actually prevent the wound from healing by blocking MMP-8’s healing properties. (R)-ND-336 inhibits only MMP-9, preserving the beneficial effects of MMP-8. This makes it a superior drug in diabetic wound healing. “We synthesized hundreds of inhibitors with different selectivity, and tested these compounds to figure out which one works better,” Chang said. “We found (R)-ND-336 is the best.” They tested the presence of the target MMP-9 enzyme by collecting wound tissue that patients from Elkhart General Hospital donated for research. Chang and Mobashery determined that the most severe and infected wounds had higher levels of this detrimental enzyme, an observation that underscores the likely success in the future human trials. Mobashery expects the latest funding will take them over the so-called Valley of Death, but more funds will need to be raised for the compound to undergo the first round of clinical trials.   Contact: Jessica Sieff, assistant director of media relations, 574-631-3933, jsieff@nd.edu Posted In: Research Home Experts ND in the News Subscribe About Us Related October 05, 2022 Astrophysicists find evidence for the presence of the first stars October 04, 2022 NIH awards $4 million grant to psychologists researching suicide prevention September 29, 2022 Notre Dame, Ukrainian Catholic University launch three new research grants September 27, 2022 Notre Dame, Trinity College Dublin engineers join to advance novel treatment for cystic fibrosis September 22, 2022 Climate-prepared countries are losing ground, latest ND-GAIN index shows For the Media Contact Office of Public Affairs and Communications Notre Dame News 500 Grace Hall Notre Dame, IN 46556 USA Facebook Twitter Instagram YouTube Pinterest © 2022 University of Notre Dame Search Mobile App News Events Visit Accessibility Facebook Twitter Instagram YouTube LinkedIn