Grant: Collaborative Health Research Projects

Arthritic diseases affect 15 % of the population and bone cancer is a frequent metastatic side*effect of the most common breast and prostate cancer. Aside from human suffering enormous*financial health care costs are added to the treatment of these diseases. Current treatments*have various shortcomings and side effects, which include increased cancer risks, atypical*fractures, bone necrosis, infections, and vascular problems. There is clearly a need for more*effective and safer treatments. Unfortunately, little progress has been made in recent years.*Most treatments attack rather non-specifically entire cells or block complex pathways, which*is likely causing the side effects. In contrast, the protease, cathepsin K, is solely responsible*for the bone degradation and significantly contributes to joint erosion. Its inhibition has been*shown to effectively reduce fracture rates in post-menopausal women. However, this*treatment also had severe side effects leading to the termination of the further development of*cathepsin K inhibitors. Our research has identified and verified a novel type of cathepsin K*inhibitors without causing any of the side effects seen in clinical trials. Interestingly, a major*source of these compounds are certain Chinese herbs traditionally used in skeletal diseases.*Recently, we have shown the efficacy of one of these compounds in an osteoporosis model*without any observable side effects. This project will expand this approach and will generate*more potent and druggable derivatives from the herbal compounds. Compounds will be*analyzed in arthritis and bone cancer mouse models. We anticipate that these compounds will*have a superior efficacy with no or fewer side effects than current treatment regimes. This*project requires a strong interdisciplinary collaboration between chemists, pharmaceutical*scientists, biochemists, and animal model researchers and will provide an excellent*opportunity for the training of students.