Preventing Adverse Effects Of Matrix Metalloproteinases In Diabetic Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$387,784.00
Summary
Treatment of diabetic foot ulcers presents a significant challenge to diabetic patients and the health care system. Despite concerted treatment, many ulcers do not heal and it is this failure to heal which eventually leads to deep-seated infection and amputation. For these reasons development of new therapeutic strategies to improve wound healing in diabetes is of critical importance. In this study we investigate the role of MMPs in particular MMP-9 in diabetic wounds and examine whether MMP inh ....Treatment of diabetic foot ulcers presents a significant challenge to diabetic patients and the health care system. Despite concerted treatment, many ulcers do not heal and it is this failure to heal which eventually leads to deep-seated infection and amputation. For these reasons development of new therapeutic strategies to improve wound healing in diabetes is of critical importance. In this study we investigate the role of MMPs in particular MMP-9 in diabetic wounds and examine whether MMP inhibition will improve wound healing in diabetes.Read moreRead less
Activin Type II Receptor Antagonists: Mechanism Of Action And Biological Applications
Funder
National Health and Medical Research Council
Funding Amount
$507,270.00
Summary
Activin is a member of the TGF- family of growth and differentiation factors. Over-expression in mice leads to muscle and liver wasting, scarring during wound healing, disturbances to the reproductive system and various endocrine disorders. Activin's biological activity is promoted by its binding in series to two receptors termed Type I and II. Previous studies by this investigator have shown that selective modification of activin's protein structure can result in activin forms (in this instance ....Activin is a member of the TGF- family of growth and differentiation factors. Over-expression in mice leads to muscle and liver wasting, scarring during wound healing, disturbances to the reproductive system and various endocrine disorders. Activin's biological activity is promoted by its binding in series to two receptors termed Type I and II. Previous studies by this investigator have shown that selective modification of activin's protein structure can result in activin forms (in this instance called activin-M108A) which bind to Type II receptors but fail to promote binding to the Type I receptor. This has led to the hypothesis that activin-M108A may compete for native activin binding to Type II receptors and thus prevent activin's recruitment of the Type I receptor with the consequence that activin's biological activity is inhibited. It is proposed to test this hypothesis by producing sufficient amounts of activin-M108A and testing its inhibitory effects in several mouse models of liver damage, muscular degeneration and ovarian and testicular disease. If activin-M108A, or related modified forms of activin, decrease the morbidity and mortality associated with these murine diseases, then we envisage that these activin type II receptor antagonists will also be beneficial for the treatment of related human conditions.Read moreRead less