NOVEL THERAPEUTICS FOR POSTMENOPAUSAL OSTEOPOROSIS

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DESCRIPTION (provided by applicant): Postmenopausal osteoporosis is a more dangerous disease than previously thought and is one of the most common diseases in older women. One in two women over age 50 will have an osteoporosis-related fracture during their lives, and fractures in postmenopausal women are a major cause of disability, mortality and economic burden. Although osteoporotic fractures are largely preventable, unfortunately, current pharmacological preventive drugs have certain limitations regarding their safety and/or efficacy. Obviously, there is a great need for new, safer and more effective drugs, which will, no doubt, be capable of capturing the global market share for osteoporotic therapeutics. Recently, promising candidates of such therapeutics have been developed in our laboratories, which show non-toxic signs and more efficacious ability to prevent bone mass loss and microstructural deterioration in a postmenopausal osteoporotic animal model. Significantly, these therapeutic candidates act on new disease targets and are able to inhibit bone resorption and possibly to stimulate bone formation as dual functional agents for preventing bone loss. These agents have been recently protected by a US patent, which will be licensed to the grant applicant for further development towards various therapeutic uses. The aim of this phase I study is to further define the candidates' ability to systematically protect bones from osteoporosis in the aforementioned animal model, thus laying a concrete foundation for the following phase II study. To reach this aim: First, the candidate agents will be prepared and their chemical structures and purity will be characterized based on our established methods; second, the postmenopausal osteoporotic animal model will be obtained and treated with the agents, as well as estrogen and bisphosphonates for comparison, using standard operative and treatment protocols already used in our laboratories; third, different bone samples (e.g. femur, humerus, mandible, tibia and vertebra) in the animals will be collected after treatment and the treatment efficacy will be evaluated using various advanced techniques, including electron paramagnetic resonance, micro-computed tomography and bone histomorphometric technologies, which have been developed and/or routinely used in our laboratories. Our multidisciplinary team with all the expertise necessary to accomplish this project is the only one working on this new kind of drug development. We believe that systematic definition of the therapeutic efficacy and further development of the candidate agents will lead to new, safer and more efficacious therapeutics, thus providing profound impacts on osteoporotic prevention and treatment and winning the considerable global market share. PUBLIC HEALTH RELEVANCE: There is a greatly unmet need for developing new osteoporotic therapeutics because of raising concerns over the current drugs' efficacy and their long-term safety. Additionally, the large number of current patients with postmenopausal osteoporosis and the worldwide growth in elderly population provide new safer and more efficacious drugs with ample opportunities to capture considerable share in the global markets for osteoporotic therapeutics. Currently, our studies have found a new kind of agent that may be the suitable candidates of such therapeutics. The agents act on new disease targets, and more effectively prevent bone loss without toxic signs. The mechanism underlying the bone protection of the agents is due to reducing bone resorption and perhaps increasing bone formation. We believe that further defining and developing these agents will lead to new dual action drugs with safer and more efficacious profiles for osteoporotic prevention and treatment.