ENHANCEMENT OF LUMBAR FUSION W/ RHBMP 2/ COLLAGEN OR LMP

使用 RHBMP 2/胶原蛋白或 LMP 增强腰椎融合

• 批准号: 7562496
• 负责人: SCOTT D. BODEN
• 金额: $ 3.16万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562496
• 关键词: Ceramics; Clinical; Clinical Trials; Collagen; Complication; Computer Retrieval of Information on Scientific Projects Database; Dose; Drug Formulations; Failure; Funding; Genetic Engineering; Grant; Growth Factor; Healed; Human; Implant; Institution; Invasive; Modeling; Monkeys; Oryctolagus cuniculus; Osteogenesis; Paste substance; Primates; Recombinants; Research; Research Personnel; Resistance; Resources; Site; Source; Speed; Spinal Fusion; Testing; Titanium; United States Food and Drug Administration; United States National Institutes of Health; Vertebral column; Work; bone; bone morphogenetic protein 2; bone morphogenetic protein 7; follow-up; healing; nonhuman primate

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. Lumbar spinal fusion is commonly performed in humans but the failure of bone union is a frequent complication. Osteoinductive growth factors synthesized by recombinant DNA technology have been shown to induce bone formation in heterotopic sites. Recombinant human BMP-2 (rhBMP-2) has been effective in generating spine fusions in a rabbit model. To determine the dose of the growth factor in humans and to determine the speed of healing, a non-human primate model is used. Higher doses than expected were required to make bone in the primate. The growth factor was delivered inside a hollow titanium threaded fusion cage through a minimally invasive approach. This work resulted in the initiation of a human pilot clinical trial with excellent results at one year follow up. Studies have focused on fine tuning the dose and studying alternative carrier materials including different combinations of ceramic materials for use in the posterolateral spine. We investigated new carriers for BMP-2 and continued studies with LMP-1 and we found that a compression resistant collagen matrix was an effective carrier and this will move on to human trials. Monkeys implanted with rhBMP-2 with a slower release carrier (paste form) and these results demonstrated that the paste was not as effective as previous carriers. In 2006 we tested a proposed clinical formulation of rhBMP-2 and compared it to an earlier formulation that was used in a successful clinical trial. This test demonstrated that the proposed formulation was not as active as the original formulation and resulted in a revised strategy for seeking FDA approval. A second study will directly compare the efficacy of rhBMP-2 to a similar BMP-7 product.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 腰椎融合术是人类的常见手术，但骨愈合失败是一种常见的并发症。通过重组DNA技术合成的骨诱导生长因子已显示在异位部位诱导骨形成。 重组人BMP-2（rhBMP-2）已在兔模型中有效地产生脊柱融合。 为了确定人类中生长因子的剂量和确定愈合速度，使用非人灵长类动物模型。灵长类动物需要比预期更高的剂量才能生成骨骼。 通过微创方法将生长因子输送到中空钛螺纹融合器内。 这项工作导致了人类试点临床试验的启动，在一年的随访中取得了优异的结果。研究集中在微调剂量和研究替代载体材料，包括用于后外侧脊柱的不同陶瓷材料组合。 我们研究了BMP-2的新载体，并继续研究LMP-1，我们发现抗压胶原基质是一种有效的载体，这将进入人体试验。 猴植入rhBMP-2和缓释载体（糊剂形式），这些结果表明糊剂不如以前的载体有效。 2006年，我们测试了rhBMP-2的拟议临床制剂，并将其与成功临床试验中使用的早期制剂进行了比较。 该试验表明，拟定制剂的活性不如原始制剂，因此需要修订策略以寻求FDA批准。 第二项研究将直接比较rhBMP-2与类似BMP-7产品的疗效。