23.3 Analysis of wound exudate matrix metalloproteinase (MMP) reductions in human chronic wounds following treatment with a novel MMP-inhibiting dressing
A.L. Brown; R.K. Ho; C.E. Hamer; G.A. Skarja; M.V. Sefton; M.H. May;
Rimon Therapeutics Ltd, Toronto, Ontario
Dysregulated MMP activity leading to excessive tissue destruction is a characteristic feature of chronic wounds. To address this problem, a novel MMP-inhibiting wound dressing* was developed, which selectively binds and removes active MMPs from the wound environment.
Dressing efficacy, determined by reduction in wound exudate MMP activity, was evaluated in a 32-subject study with various chronic wound types. After 2 weeks of baseline treatment with practitioner's standard of care (SOC), patients were randomized to 4 weeks of treatment with either the MMP-inhibiting dressing or SOC. Dressings were collected weekly and exudates extracted for analysis. MMP activity was determined using a broad-spectrum chromogenic substrate assay, while MMP-8 concentration (by ELISA) was measured as a marker of inflammation. All measurements were normalized for sampled exudate mass and protein concentration.
Global treatment efficacy was evaluated using regression analysis on the weekly MMP activity versus MMP-8 concentration data. At baseline, these 2 parameters were strongly correlated. Following treatment with the MMP-inhibiting dressing, regression line slopes were significantly reduced compared to baseline and control data (P < 0.0005), indicating a reduction in the active MMP fraction within the treated wounds.
To correct for changes in inflammatory status, patient MMP activity profiles were expressed relative to MMP-8 concentrations using an Òequivalence factorÓ calculated at baseline. Significant reductions in adjusted MMP activities versus baseline were observed for treated wounds, while controls remained unchanged. These results correlated well with histological improvements in wound bed quality validating the effectiveness of active MMP targeting for the treatment of chronic wounds.
*MI-Sorb Dressingª, Rimon Therapeutics Ltd, Toronto, Canada
