application): The single specific aim of this Phase I proposal is to test the hypothesis that the potent kallikrein inhibitor EPI-K503 can prevent and/or treat PG-APS-induced inflammatory arthritis and its associated systemic inflammation. The rationale for this proposal is that specific inhibition of the enzyme kallikrein will block its effects to worsen inflammatory changes. The planned inhibitor is a peptide analogous to aprotinin that will be injected into an established rat model of acute and chronic relapsing inflammatory erosive arthritis, with appropriate controls. Inflammatory changes in joints and systemic measures of inflammation will be assessed. If the inhibitor is successful in decreasing the arthritis and systemic inflammation, there are plans for a Phase II study to develop non-peptide inhibitors of the enzyme with related structures, and to test these in a model of inflammatory bowel disease.
NOT AVAILABLE
| Uknis, A B; DeLa Cadena, R A; Janardham, R et al. (2001) Bradykinin receptor antagonists type 2 attenuate the inflammatory changes in peptidoglycan-induced acute arthritis in the Lewis rat. Inflamm Res 50:149-55 |
| Colman, R W (1999) Plasma and tissue kallikrein in arthritis and inflammatory bowel disease. Immunopharmacology 43:103-8 |
