MONOCLONAL ANTIBODIES FOR OSTEOPOROSIS RESEARCH

DESCRIPTION (provided by applicant): Osteoporosis is a major health problem affecting nearly 1.5 million people every year. The reduction of sex hormone levels in both men and women increase production of certain factors that lead to osteoporosis. One-third of all menopausal women experience at least one osteoporotic fracture during their lifetime. In addition, certain malignancies, including breast, prostrate, or lung frequently metastasize to long bones, spinal vertebrae, and/or pelvis. Primary and metastatic cancers involving bone account for approximately 400,000 new cancer cases per year in the United States alone, and >70% of patients with advanced breast or prostate cancer have skeletal metastases. Ongoing osteoclastic activity appears to be involved in the generation and maintenance of ongoing and movement-evoked pain. Recently, several protein factors, such as RANK, RANKL, and OPG have been identified that are important in the pathogenesis of disease. RANKL by binding to cell surface receptor RANK on the osteoclastic precursor cells induce formation of osteoclasts, which are involved in bone resorption. Administration of OPG (which acts as decoy receptor for RANKL) has been shown to halt further bone destruction, reduce a ongoing and movement-evoked pain. Blockade of ongoing osteoclast activity of RANKL by inhibitory molecules have the potential to reduce bone cancer pain in patients with advanced tumor-induced bone destruction. Since OPG/RANKL ratio play an important role osteoclast development, it is important to monitor the levels of RANKL and OPG in patients' blood circulation. In this Phase II study, using monoclonal antibodies, we propose to develop sensitive assays to measure OPG and RANKL in blood stream. We also propose to develop monoclonal antibodies that can neutralize RANKL activity in the development of osteoclasts, These monoclonal antibodies will have therapeutic application.