MONOCLONAL ANTIBODIES FOR OSTEOPOROSIS RESEARCH

骨质疏松症是一个主要的健康问题，每年影响近150万人。三分之一的绝经后白人女性在其一生中至少经历过一次骨质疏松性骨折。男性和女性性激素水平的降低会增加导致骨质疏松症的某些因素的产生。破骨细胞和成骨细胞活性之间的不平衡导致代谢性疾病，如骨质疏松症（骨量减少）和骨硬化症（骨量增加）。最近，两个可溶性和一个膜结合因子在调节破骨细胞分化和功能中起重要作用被确定。这些包括骨保护素配体（OPGL）、RANK（OPGL的膜结合受体）和骨保护素（OPG; OPGL的可溶性受体）。几项研究表明，OPGL通过RANK诱导破骨细胞形成，导致骨质疏松症，而OPG可预防骨质疏松症。目前，没有试剂可用于测量这些蛋白质在体内的水平。在拟定的I期研究中，我们将开发用于高灵敏度酶联免疫测定的单克隆抗体，以定量这些因子。我们还将选择能够中和破骨细胞的骨吸收活性的单克隆抗体。我们的II期研究将在动物模型中测试这些试剂。这些单克隆抗体将成为骨质疏松症研究的重要工具。建议的商业应用：骨质疏松症是衡量男性和女性健康问题的一个标准。性激素水平下降是骨质疏松症的原因之一。近年来，一些蛋白质因子已被确定在疾病的发病机制中是重要的。目前没有试剂可用于测量这些蛋白质在体内的水平。在本I期研究期间开发的单克隆抗体将是用于测量生物样品中这些蛋白质的有价值的工具。这些抗体在预防骨质疏松症方面也可能具有临床意义。我们预计这些试剂的市场将是巨大的。

Osteoporosis is a major health problem affecting nearly 1.5 million people every year. One-third of all post-menopausal Caucasian women experience at least one osteoporotic fracture during their lifetime. The reduction of sex hormone levels in both men and women increases production of certain factors that lead to osteoporosis. An imbalance between osteoclast and osteoblast activities causes metabolic diseases as osteoporosis (decreased bone mass) and osteopetrosis (increased bone mass). Recently, two soluble and one membrane-bound factors that play important roles in modulating osteoclast differentiation and function were identified. These include Osteoprotegerin ligand (OPGL), RANK (a membrane-bound receptor for OPGL), and Osteoprotegerin (OPG; a soluble receptor for OPGL). Several studies have shown that OPGL acts through RANK to induce osteoclast formation leading to osteoporosis, whereas OPG prevents osteoporosis. Presently, there are no reagent available to measure the levels of these proteins in vivo. In the proposed Phase I study, we will develop monoclonal antibodies for use in a highly sensitive enzyme linked immunoassay to quantitate these factors. We will also select monoclonal antibodies that can neutralize bone resorption activity of osteoclasts. Our Phase II study will test these reagents in animal models. These monoclonal antibodies will be valuable tools for osteoporosis research. PROPOSED COMMERCIAL APPLICATIONS: Osteoporosis is a measure health problem in men and women. A decrease in sex hormone level is one of the cause of osteoporosis. Recently several protein factors have been identified that are important in pathogenesis of disease. Presently no reagents are available, which can measure the levels of these proteins in vivo. Monoclonal antibodies developed during this Phase I study will be valuable tools for measurement of these proteins in biological samples. These antibodies may also have clinical significance in preventing osteoporosis. We expect the market for these reagents to be vast.