Inhibitors of RANK and RANKL in Osteoporosis Treatment

描述（由申请人提供）：骨质疏松症是一个主要的健康问题 每年影响近150万人性激素减少 男性和女性的水平都增加了某些因素的产生， 骨质疏松症三分之一的绝经后白人女性在 最小的骨折。此外，70多名 患有晚期乳腺癌或前列腺癌的患者中， 由于破骨细胞生成导致骨降解的转移。正在进行 破骨细胞活性似乎参与了 持续性和运动诱发性疼痛。持续破骨细胞活性的阻断 似乎有可能减少骨癌患者的疼痛， 晚期肿瘤导致的骨质破坏最近的研究表明，RANKL， 肿瘤坏死因子超家族的一员，通过其 RANK受体可诱导破骨细胞形成，导致骨质疏松症。在 在本研究中，我们建议通过筛选肽来鉴定肽抑制剂， 显示库。这些肽干扰RANKL的能力 将测试诱导的破骨细胞形成。选择的抑制作用 将在II期研究中测试动物模型中的肽。所选 肽可用于设计甚至更小的肽或小分子 非肽模拟物，其可用作治疗药物。

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 post-menopausal Caucasian women experience at least osteoporotic fracture during their lifetime. In addition, more than 70 percent of patients with advanced breast or prostate cancer have skeletal metastases leading to bone degradation due to osteoclastogenesis. Ongoing osteoclast activity appears to be involved in the generation and maintenance of ongoing and movement-evoked pain. Blockade of ongoing osteoclast activity appears to have the potential to reduce bone cancer pain in patients with advanced tumor-induced bone destruction. Recent studies have shown that RANKL, a member of the tumor necrosis factor superfamily, by acting through its receptor RANK can induce osteoclast formation leading to osteoporosis. In the present study, we propose to identify peptide inhibitors by screening peptide display libraries. The ability of these peptides to interfere with RANKL induced osteoclast formation will be tested. The inhibitory effect of selected peptides in animal models will be tested in the Phase II study. The selected peptides can be used to design even smaller peptides or small molecule non-peptide mimetics, which can be used as therapeutic drugs.