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: 7715661
• 负责人: SCOTT D. BODEN
• 金额: $ 2.85万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715661
• 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; Variant; Vertebral column; Work; bone; bone growth factor; 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 were 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. In 2007 we compared the efficacy of rhBMP-2 to a similar product (BMP-7). We did not find the formulation of BMP-7 to be as effective as BMP-2 for spine fusion. We also performed a comparison with GDF-5, another variant bone growth factor.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 腰椎融合通常在人类中进行，但骨骼联合的失败是常见的并发症。通过重组DNA技术合成的骨诱导生长因子已显示出在异位部位诱导骨形成。 重组人BMP-2（RHBMP-2）在兔模型中产生脊柱融合已有效。 为了确定人类生长因子的剂量并确定愈合速度，使用了非人类灵长类动物模型。在灵长类动物中造成骨骼需要的剂量高于预期。 生长因子通过微创方法在空心的钛螺纹融合笼中传递。 这项工作导致了一项人类试验临床试验的启动，并在一年的随访中取得了出色的成绩。研究集中在微调剂量和研究替代载体材料上，包括不同的陶瓷材料组合，用于后外侧脊柱。 我们研究了BMP-2的新载体，并继续对LMP-1进行研究，我们发现耐压缩胶原蛋白基质是有效的载体，这将继续进行人类试验。 将猴子植入RHBMP-2的释放载体（糊状形式），这些结果表明糊状物不如以前的载体有效。 在2006年，我们测试了RHBMP-2的临床临床制定，并将其与成功临床试验中使用的较早配方进行了比较。 该测试表明，所提出的配方不像原始配方那样活跃，并制定了寻求FDA批准的修订策略。 在2007年，我们将RHBMP-2的功效与类似产品（BMP-7）进行了比较。我们没有发现BMP-7的配方对脊柱融合的有效性与BMP-2一样有效。 我们还与GDF-5进行了比较，GDF-5是另一个变异的骨生长因子。