Development of a novel therapeutic for osteoporosis

骨质疏松症新疗法的开发

• 批准号: MR/J014621/1
• 负责人: Anthony Day
• 金额: $ 84.38万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ014621%2F1
• 关键词: Development; novel; therapeutic; osteoporosis

Osteoporosis, which affects a large proportion of the elderly population, frequently results in bone fractures due to uncontrolled bone loss; 1 in 2 women and 1 in 5 men over the age of 50 will experience an osteoporosis-related fracture during their lifetime. This severely impacts on quality of life and 20-30% of hip fractures lead to death within 12 months. There is currently no ideal treatment for osteoporosis due to side effects and problems associated with their long-term use, e.g. atypical fractures of the hip and immune suppression resulting in infections. Poor compliance (due to these side effects and under diagnosis) is a significant problem and consequently treatment rates are less than 20% throughout the world. Most importantly osteoporosis is a long-term condition that requires long-term therapy, i.e. up to several decades. Therefore, there is a growing clinical need for the development of new therapies to provide additional treatment options to allow better management of this common, debilitating and potentially fatal condition.We have identified a molecule that is a potent inhibitor of bone loss, which we propose to develop as a novel treatment for osteoporosis. This drug candidate is derived from a human protein that has a role in the normal regulation of bone turnover. We anticipate that this protein will have limited undesirable side effects (unlike existing therapies), thus enabling its long-term use (and improving compliance). This project will build on our preliminary data and is aimed at establishing an optimal treatment protocol in an approved experimental model of post-menopausal osteoporosis; initial safety testing will also be carried out. This preclinical evaluation will inform and facilitate future studies, including trials in humans, and help us obtain a commercial partner with whom to co-develop our technology.

骨质疏松症影响大部分老年人口，由于不受控制的骨质流失，经常导致骨折; 50岁以上的2名女性中有1名和5名男性中有1名将在其一生中经历骨质疏松症相关的骨折。这严重影响了生活质量，20-30%的髋部骨折在12个月内导致死亡。由于与长期使用相关的副作用和问题，目前还没有理想的骨质疏松症治疗方法，例如非典型髋关节骨折和导致感染的免疫抑制。依从性差（由于这些副作用和诊断不足）是一个严重的问题，因此全世界的治疗率不到20%。最重要的是，骨质疏松症是一种长期疾病，需要长期治疗，即长达几十年。因此，临床上越来越需要开发新的治疗方法，以提供更多的治疗选择，从而更好地管理这种常见的、使人衰弱的和潜在的致命性疾病。我们已经确定了一种分子，它是一种有效的骨丢失抑制剂，我们建议开发为骨质疏松症的新治疗方法。这种候选药物来源于一种在骨转换的正常调节中起作用的人类蛋白质。我们预计这种蛋白质将具有有限的不良副作用（与现有疗法不同），从而使其能够长期使用（并提高依从性）。 该项目将建立在我们的初步数据基础上，旨在建立经批准的绝经后骨质疏松症实验模型的最佳治疗方案;还将进行初步安全性测试。这项临床前评估将为未来的研究提供信息和促进，包括人体试验，并帮助我们获得商业合作伙伴，与他们共同开发我们的技术。

项目成果

The Anti-inflammatory Protein TSG-6 Regulates Chemokine Function by Inhibiting Chemokine/Glycosaminoglycan Interactions.

• DOI: 10.1074/jbc.m116.720953
• 发表时间: 2016-06-10
• 期刊: The Journal of biological chemistry
• 作者: Dyer DP;Salanga CL;Johns SC;Valdambrini E;Fuster MM;Milner CM;Day AJ;Handel TM
• 通讯作者: Handel TM