Researchers led by Mayland Chang, previously identified two enzymes called matrix metalloproteinases (MMPs), MMP-8 and MMP-9, in the wounds of diabetic mice. They proposed that the former might play a role in the body's response to wound healing and the latter was the pathological consequence of the disease with detrimental effects. The researchers used the MMP-9 inhibitor referred to as ND-322, which accelerated wound healing in diabetic mice.
‘Currently, there are limited therapeutic agents that could accelerate or facilitate the healing of diabetic wounds. Discovery of a new compound could accelerate diabetic wound healing, and may open the door to new treatment strategies.’
In a new study that appears in the Proceedings of the National Academy of Sciences
, the researchers report the discovery of a better MMP-9 inhibitor referred to as ND-336. Chang said, "ND-336 is a six-fold more potent inhibitor than ND-322 and has 50-fold selectivity towards inhibition of MMP-9 than MMP-8. In contrast, ND-322 has three-fold selectivity towards inhibition of MMP-9 compared to MMP-8. The current paper compared the efficacy of ND-336 versus ND-322. We found that wounds treated with ND-336 healed significantly faster than those treated with ND-322 because of the better selectivity of ND-336 than ND-322 for inhibition of MMP-9 over MMP-8. In the current paper we applied the enzyme MMP-8 to wounds of diabetic mice and found accelerated wound healing. We also combined the MMP-9 inhibitor ND-336 and the enzyme MMP-8 and found further acceleration of diabetic wound healing."
The researchers found that a combination of a selective inhibitor of MMP-9 (a small molecule) and applied MMP-8 (an enzyme) enhanced healing even more, in a strategy that holds considerable promise in healing of diabetic wounds.
Chang said, "The compound ND-336 has potential as a therapeutic to accelerate or facilitate wound healing in diabetic patients. Likewise, the enzyme MMP-8 could be used to accelerate/facilitate diabetic wound repair. The combination of a small molecule (ND-336) and the enzyme MMP-8 has the potential to accelerate further diabetic wound repair."
The researchers are currently recruiting diabetic patients to ascertain the levels of MMP-8 and MMP-9 in their wounds. This study is in collaboration with the Center for Wound Healing at Elkhart General Hospital.