RHPDGF-BB IRHPDGF-BB IN VERTEBRAL BODIES OF BABOONS RECEIVING IV BIOPHOSDHONATE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本研究的目的是评估将一种名为GEM-OS2的生长因子蛋白(GEM-OS2)与胶原/P-磷酸三钙糊剂(P-TCP)混合在一起注入狒狒椎体的安全性和有效性。GEM-OS2是血小板衍生生长因子-BB(rhPDGF-BB)的产品名称。预计将这种材料注射到狒狒的脊椎中将被证明是安全的，即没有任何与神经和骨组织有关的不良后果或毒性。此外，预计在静脉注射双膦酸盐的情况下，将重组人PDGF-BB与胶原-磷酸三钙基质结合注入椎体，防止骨吸收，将导致治疗骨密度的统计显著增加(大于或等于5%的增加)。这些动物将在接受治疗后定期观察行为或正常行动能力的任何变化。非侵入性成像技术(例如，X射线照片、磁共振成像(MRI))将用于监测治疗后脊椎骨骼和周围软组织的结构，以确保治疗后不会出现异常组织生长。用于测量骨形成量的附加成像技术(双能X射线吸收测量仪(DEXA)和定量计算机断层扫描(QCT))将被用来评估治疗在提高老年狒狒骨密度方面的效果，类似于对人类患者的操作。将监测血清中指示正常骨代谢的分子，以确保注射不会导致新陈代谢发生异常变化。 骨质疏松症是一种人类患者随着时间的推移骨密度显著下降，并导致脊柱椎体压缩骨折的疼痛和虚弱的情况。随着美国老年人口的不断增加，非常需要治疗或逆转骨质疏松症影响的疗法。GEM-OS2TM产品旨在注射到椎体内，我们预计它将导致该位置的骨骼增大，并减少骨质疏松症患者经历的骨折数量。GEM OS2TM在狒狒模型上的测试将证明它可以安全地使用，并证明了它在治疗后增加骨密度的有效性。这项研究的成功将导致该产品在人类骨质疏松症患者中进行临床试验测试。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to evaluate the safety and efficacy of injecting a growth factor protein known as GEM-OS2 which is the product name for a platelet-derived growth factor-BB (rhPDGF-BB) mixed with a collagen/P-tricalcium phosphate paste (P-TCP), into the vertebral bodies of baboons. It is expected that injection of this material into the spine of the baboons will prove to be safe, that is, free of any adverse outcomes or toxicity relating to the nervous and bone tissues. In addition, it is expected that injection of rhPDGF-BB combined with a collagen-TCP matrix into the vertebral bodies with IV administration of a bisphosphonate, which prevents bone resorption, will lead to a statistically significant increase in the density of the treated bones (greater than or equal to 5% increase). The animals will be observed regularly following treatment for any changes in behaviour or ability to move normally. Non-invasive imaging techniques (for example, x-ray radiographs, magnetic resonance imaging (MRI)) will be used to monitor the structure of the treated vertebral bones and surrounding soft tissues to ensure that no abnormal tissue growth occurs following the treatments. Additional imaging techniques (dual-energy x-ray absorptiometry (DEXA) and quantitative computed-tomography (qCT)) used for measuring the amount of bone formed will be employed to evaluate the efficacy of the treatments in increasing bone density in the aged baboons, similarly to what would be performed for a human patient. Molecules in serum indicative of normal bone metabolism will be monitored to ensure no abnormal changes in metabolism occur as a result of the injections. Osteoporosis is a condition in which human patients experience a significant loss of bone mineral density over time, and leads to painful and debilitating compression fractures of the vertebral bodies of the spine. With an ever-increasing geriatric population in the United States, there is a great need for therapies that will treat or reverse the effects of osteoporosis. The GEM-OS2TM product is intended for injection into the vertebral bodies where we expect it will lead to augmentation of the bone in this location and reduce the number of fractures experienced by osteoporosis patients. The testing of GEM OS2TM in the baboon model will demonstrate that it can be administered safely, and demonstrate its efficacy in augmenting bone mineral density following treatment with the material. The success of this study will lead to clinical trial testing for the product in osteoporotic human patients.