The Department of Defense has funded a compound developed at the University Notre Dame to help the university avoid the “Valley of Death”—the dangerous zone in drug development that represents the gap between discovery and clinical research. Promising compounds often die here.
The University of Notre Dame’s compound, known as (R)-ND-336, is a topical gel for the treatment of diabetic foot ulcers. Developed by research professor Mayland Chang with the Department of Chemistry and Biochemistry and Shahriar Mobashery, the Navari Family Professor in Life Sciences in the Department of Chemistry and Biochemistry. Both investigators are affiliated with Advanced Diagnostics & Therapeutics and the Warren Family Research Center for Drug Discovery and Development. (R)-ND-336 was compared to the existing approved product, becaplermin, and it was shown to be superior.
The University of Notre Dame investigators reviewed specific enzymes known as matrix metalloproteinases (MMPs), involved in remodeling tissues, and in the process uncovered that the two closely related MMPs played roles in diabetic wound healing. MMP-9 actually slows healing while MMP-8 promotes healing. (R)-ND-336 inhibits only MMP-9, hence preserving the beneficial effects of MMP-8. This makes it a superior drug in diabetic wound healing.
The Problem: Diabetic Foot Ulcers
25 percent of diabetes patients will development foot ulcers. Notoriously difficult to heal, they are triggered by elevated blood glucose causing numbness in the extremities—and patients typically cannot feel the ulcers.
The Problem with becaplermin
The only FDA-approved drug on the market to treat diabetic ulcers, this drug was introduced 20 years ago. Utilizing a growth factor to stimulate tissue healing and moderately effective, it comes with a black box warning for an increase in cancer and death.
The DoD Funding
The $4.6 million will help fund the expensive studies required prior the compound can be given approval by the FDA to be tested on people. The two University of Notre Dame investigators expect the pre-clinical phase to last two years, and both anticipate the compound to move forward to human clinical trials. In existing preclinical studies, they have shown that it should not cause cancer or trigger other toxic side effects.
Mayland Chang, with the Department of Chemistry and Biochemistry
Shahriar Mobashery, the Navari Family Professor in Life Sciences in the Department of Chemistry and Biochemistry
Call to Action: With the DoD funding, this University of Notre Dame preclinical compound has a chance of surviving the “Valley of Death.” If you are interested in tracking (R)-ND-336, sign up for the Daily Newsletter.