NOVEL THERAPEUTICS FOR POSTMENOPAUSAL OSTEOPOROSIS

绝经后骨质疏松症的新疗法

• 批准号: 8251439
• 负责人: GANG LIU
• 金额: $ 18.77万
• 依托单位: NANOMEDIC, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8251439
• 关键词: Adverse effects; Aftercare; Age; Am 80; Animal Model; Animals; Biological Assay; Bone Diseases; Bone Resorption; Chelating Agents; Chemical Structure; Data; Deterioration; Development; Disease; Drug effect disorder; Dual-Energy X-Ray Absorptiometry; Economic Burden; Effectiveness; Elderly; Electron Spin Resonance Spectroscopy; Estrogens; Femur; Ferritin; Foundations; Fracture; Free Radical Formation; Goals; Grant; Growth; Imaging technology; International; Iron; Laboratories; Lead; Legal patent; Licensing; Malignant neoplasm of esophagus; Mandible; Marketing; Measurement; Methods; Modeling; Osteogenesis; Osteopenia; Osteoporosis; Patients; Peripheral; Pharmaceutical Preparations; Population; Postmenopausal Osteoporosis; Postmenopause; Prevention; Preventive; Rattus; Risk; Safety; Sampling; Serum; Site; Structure; Techniques; Technology; Therapeutic; Therapeutic Uses; Toxic effect; Treatment Efficacy; Treatment Protocols; Uncertainty; Universities; Utah; Vertebral Bone; Woman; Work; X-Ray Computed Tomography; aged; base; bisphosphonate; bone; bone loss; bone mass; chelation; commercialization; disability; drug development; drug efficacy; drug standard; hormone therapy; humerus; mortality; multidisciplinary; novel; novel therapeutics; older women; osteoporosis with pathological fracture; oxidative damage; phase 1 study; phase 2 study; prevent; response; spine bone structure; tibia

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.

描述（由申请人提供）：绝经后骨质疏松症是一种比以前想象的更危险的疾病，也是老年女性最常见的疾病之一。 50 岁以上的女性中，有二分之一会在一生中发生与骨质疏松症相关的骨折，而绝经后女性的骨折是导致残疾、死亡和经济负担的主要原因。尽管骨质疏松性骨折在很大程度上是可以预防的，但不幸的是，目前的药理学预防药物在其安全性和/或功效方面存在一定的局限性。显然，我们非常需要新的、更安全、更有效的药物，毫无疑问，这些药物将能够占领骨质疏松治疗的全球市场份额。最近，我们的实验室开发了此类疗法的有前途的候选药物，它们在绝经后骨质疏松动物模型中显示出无毒迹象和更有效的预防骨质流失和微结构恶化的能力。值得注意的是，这些候选治疗药物作用于新的疾病靶点，能够抑制骨吸收，并可能刺激骨形成，作为预防骨质流失的双重功能剂。这些药物最近受到美国专利的保护，该专利将授权给资助申请人，以进一步开发各种治疗用途。本次一期研究的目的是进一步明确候选者在上述动物模型中系统地保护骨骼免受骨质疏松的能力，从而为后续二期研究奠定坚实的基础。为了实现这一目标：首先，将制备候选药物，并根据我们既定的方法表征其化学结构和纯度；其次，将使用我们实验室已使用的标准手术和治疗方案获得绝经后骨质疏松动物模型，并用药物以及雌激素和双膦酸盐进行治疗以进行比较；第三，治疗后收集动物的不同骨骼样本（例如股骨、肱骨、下颌骨、胫骨和椎骨），并利用各种先进技术评估治疗效果，包括电子顺磁共振、微型计算机断层扫描和骨组织形态测量技术，已在我们的实验室中开发和/或常规使用。我们的多学科团队拥有完成该项目所需的所有专业知识，是唯一致力于这种新型药物开发的团队。我们相信，对治疗功效的系统定义和候选药物的进一步开发将带来新的、更安全、更有效的治疗方法，从而对骨质疏松症的预防和治疗产生深远的影响，并赢得相当大的全球市场份额。 公众健康相关性：由于人们对现有药物的疗效及其长期安全性的担忧，开发新的骨质疏松治疗药物的需求尚未得到满足。此外，目前大量的绝经后骨质疏松症患者以及全球老年人口的增长为新的更安全、更有效的药物提供了充足的机会，以在全球骨质疏松治疗市场上占据相当大的份额。目前，我们的研究发现了一种新型药物可能是此类疗法的合适候选者。这些药物作用于新的疾病靶标，更有效地预防骨质流失，且没有毒性迹象。这些药物的骨保护机制是由于减少骨吸收并可能增加骨形成。我们相信，进一步定义和开发这些药物将带来新的双重作用药物，对于骨质疏松症的预防和治疗来说更安全、更有效。