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）：绝经后骨质疏松症比以前想象的更危险，是老年女性最常见的疾病之一。 50岁以上的两名女性一生中将出现与骨质疏松相关的骨折，绝经后妇女的骨折是残疾，死亡率和经济负担的主要原因。尽管骨质疏松性骨折基本上是可以预防的，但不幸的是，当前的药理预防性药物在其安全性和/或功效上有一定的限制。显然，需要新的，更安全，更有效的药物，毫无疑问，这将有能力捕获骨质疏松疗法的全球市场份额。最近，在我们的实验室中已经开发出了有希望的这种治疗疗法的候选者，这些候选者表现出无毒体征和更有效的能力，可预防绝经后骨质疏松动物模型中的骨骼质量损失和微结构恶化。值得注意的是，这些治疗候选者对新疾病靶标作用，并能够抑制骨吸收，并可能刺激骨形成作为预防骨质流失的双重功能剂。这些代理商最近受到美国专利的保护，该专利将获得授予申请人的许可，以进一步开发各种治疗用途。本研究研究的目的是进一步定义候选人在上述动物模型中系统地保护骨骼免受骨质疏松症的能力，从而为以下II期研究奠定了具体的基础。要达到这个目标：首先，将准备候选代理，并根据我们既定的方法来对其化学结构和纯度进行特征。其次，将使用已经在我们的实验室中使用的标准手术和治疗方案获得了绝经后的骨质疏松动物模型，以及用雌激素和双膦酸盐进行比较。第三，将在治疗后收集不同的骨样品（例如股骨，肱骨，下颌骨，胫骨和椎骨），并将使用各种先进的技术（包括已开发在我们的实验室中已经开发出已开发出已开发过的电子磁性造影术和骨骼组合技术，包括电子磁共振成像和骨骼组织力学技术，包括电子磁共振成术和骨骼组织组合技术，包括电子磁共振成术和骨骼组织组合技术。我们的多学科团队拥有完成该项目所需的所有专业知识，是唯一从事这种新型药物开发的人。我们认为，对治疗功效的系统定义和候选代理的进一步发展将导致新，更安全，更有效的治疗疗法，从而对骨质疏松预防和治疗产生深远的影响，并赢得大量全球市场份额。 公共卫生相关性：由于人们对当前药物的功效及其长期安全性提出了担忧，因此需要开发新的骨质疏松治疗剂的需求。此外，绝经后骨质疏松症的当前患者和老年人口的全球增长提供了新的更安全，更有效的药物，并有足够的机会在骨质疏松疗法的全球市场中占据相当大的份额。目前，我们的研究发现了一种新型药物，可能是这种治疗剂的合适候选者。该代理作用于新疾病靶标，并更有效地防止骨质流失而没有毒性迹象。药物保护骨保护的基础机制是由于减少了骨吸收并可能增加了骨形成。我们认为，进一步定义和开发这些药物将导致新的双重动作药物具有更安全，更有效的概况，以预防骨质疏松和治疗。