GROWTH FACTOR GENE THERAPY FOR WOUND HEALING

用于伤口愈合的生长因子基因疗法

• 批准号: 6375229
• 负责人: John Doukas
• 金额: $ 50.8万
• 依托单位: SELECTIVE GENETICS, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6375229
• 关键词: Adenoviridae; clinical research; clinical trial phase I; collagen; gene targeting; gene therapy; histology; human subject; human therapy evaluation; immunocytochemistry; laboratory rabbit; laboratory rat; nonhuman therapy evaluation; platelet derived growth factor; skin ulcer; swine; technology /technique development; transfection /expression vector; wound healing

The need for effective treatment of chronic dermal wounds is poorly met, despite yearly medical costs exceeding $1 billion. Although growth factors are logical therapeutic candidates, for the most part they have not produced clinically significant benefits. A major limitation has been maintaining therapeutic levels at treatment sites. Delivering growth factor-encoding gene therapy vectors in biocompatible matrices, however, should allow for prolonged therapeutic production and retention in treated wounds. As platelet derived growth factor (PDGF)-B is particularly suited for wound treatment, we propose to utilize an adenoviral vector encoding this gene formulated in collagen as a wound therapeutic. Specific Aim #1 will extend Phase I studies in order to select a final vector and collagen formulation, by measuring in vivo activity in an animal model. Specific Aim #2 will perform preclinical efficacy, safety, and toxicology studies in preparation for human trials. Specific Aim #3 will produce and test bulk virus for these trials. Finally, Specific Aim #4 will be a Phase I clinical study for the treatment of chronic diabetic ulcers. Successful completion of this work will then allow for progression to Phase II and III clinical studies, and commercialization of the final product. PROPOSED COMMERCIAL APPLICATIONS: Chronic dermal wounds are a significant public health concern, and yearly medical costs are estimated to exceed $1 billion. Presently, few therapeutic options allow for the augmentation of soft tissue repair, especially in patients with chronic ulcers. These studies will permit the development of novel therapeutics for wound treatment, as well as the initial evaluation of these products in human clinical trials. The combined use of gene therapy with a semi-solid matrix delivery system offers the possibility of delivering novel and potent therapeutic agents, with improved specificity and efficacy over that offered by existing treatments.

尽管每年超过10亿美元的医疗费用，但对慢性皮肤伤口进行有效治疗的需求却很差。尽管生长因子是逻辑的治疗候选者，但在大多数情况下，它们没有产生临床上的显着好处。一个主要的限制是维持治疗部位的治疗水平。但是，在生物相容性基质中提供生长因子编码基因治疗载体，应允许长时间的治疗性产生和保留在治疗的伤口中。由于血小板衍生的生长因子（PDGF）-b特别适合伤口治疗，我们建议利用编码该基因在胶原蛋白中作为伤口治疗的腺病毒载体。特定的目标＃1将扩展I期研究，以通过测量动物模型中的体内活性来选择最终的载体和胶原蛋白配方。特定的目标＃2将在为人类试验准备准备时，执行临床前功效，安全性和毒理学研究。特定的目标＃3将为这些试验产生和测试散装病毒。最后，特定的目标＃4将是I期临床研究，用于治疗慢性糖尿病性溃疡。然后，这项工作的成功完成将允许发展到II和III期临床研究，以及最终产品的商业化。拟议的商业应用：慢性皮肤伤口是一个重大的公共卫生问题，估计每年的医疗费用超过10亿美元。目前，很少有治疗选择可以增加软组织修复，尤其是在慢性溃疡患者中。这些研究将允许开发用于伤口治疗的新型治疗剂，以及在人类临床试验中对这些产品的初步评估。基因疗法与半固体基质递送系统的联合使用提供了提供新颖和有效的治疗剂的可能性，具有改善现有治疗方法的特异性和功效。