Therapeutic to Reduce Acute Inflammation in Severe Burn Injuries

减轻严重烧伤急性炎症的治疗方法

• 批准号: 7053478
• 负责人: ELISABETH M ALICOT-CARROLL
• 金额: $ 12.92万
• 依托单位: DECIMMUNE THERAPEUTICS, INC
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7053478
• 关键词: biotechnology; biotherapeutic agent; burn therapy; burns; disease /disorder model; drug design /synthesis /production; genetically modified animals; immune response; immunocytochemistry; immunoglobulin M; immunopharmacology; immunoregulation; immunosuppressive; inflammation; intravenous administration; laboratory mouse; light microscopy; phenotype; reperfusion; scars; skin disorder chemotherapy; topical drug application; wound healing

DESCRIPTION (provided by applicant): Declmmune Therapeutics is seeking support to develop a therapeutic product that will significantly reduce the debilitating and sometimes life-threatening result of severe burn injuries. Much of the final extent of tissue loss following burn injury is determined by the inflammatory response. The company has developed novel methods and compounds that inhibit inflammation at the initial site of tissue injury and significantly reduce the destruction of tissue surrounding the injury. Preliminary studies in animal models of burn injury have demonstrated a potential protective effect of one of these compounds, preventing the inflammatory destruction of skin tissue following burn trauma, resulting in healing without scarring or loss of hair growth. Over 75,000 patients per year are hospitalized for severe burn injuries, spending an average of two weeks undergoing painful and expensive treatments consisting of antibiotics, nutritionals and surgical care of the wound. The long-term objective of this project is to develop a therapeutic product that reduces the inflammatory destruction of skin tissue following burn injury and improves the outcome of the severely burned patient. Such a therapeutic could result in a wound which heals faster and with less need for skin grafting or other surgical intervention, reduce hospitalization costs and result in less permanent scarring and debilitating effects to the patient. Declmmune has developed compounds which block acute inflammation following ischemia/reperfusion injury in animal models. The objective of this proposal is to test these compounds in a mouse model of thermal burn injury with the following aims: 1) To demonstrate that one or more of these compounds is effective in improving the healing of an acute burn, 2) To determine how long after the burn injury the compound can be administered and be effective, and 3) To determine how severe a burn wound can still show improvement with the compound. The expected endpoint is the demonstration that in our animal model, one or more of these compounds can be administered immediately or shortly after a burn injury, either intravenously or topically, and the burn wound is shown to heal with significantly less scarring and loss of hair growth vs. the untreated animal. Phase II SBIR funding will support the development of the peptide compound into a drug candidate, preclinical testing and clinical evaluation in Phase I human trials.

描述（由申请人提供）：Declmmune Therapeutics正在寻求支持，以开发一种治疗产品，该产品将显着减少严重烧伤的衰弱，有时甚至危及生命的结果。烧伤后组织损失的最终程度大部分由炎症反应决定。该公司开发了新的方法和化合物，可抑制组织损伤初始部位的炎症，并显着减少损伤周围组织的破坏。在烧伤动物模型中的初步研究已经证明了这些化合物之一的潜在保护作用，防止烧伤创伤后皮肤组织的炎性破坏，导致愈合而没有瘢痕形成或毛发生长损失。每年有超过75，000名患者因严重烧伤住院，平均花费两周时间进行痛苦而昂贵的治疗，包括抗生素，营养品和伤口手术护理。该项目的长期目标是开发一种治疗产品，减少烧伤后皮肤组织的炎性破坏，改善严重烧伤患者的预后。这样的治疗剂可以导致伤口愈合更快，并且对皮肤移植或其他手术干预的需要更少，降低住院费用，并且导致对患者的永久性疤痕和衰弱效应更少。Declmmune已经开发出在动物模型中阻断缺血/再灌注损伤后的急性炎症的化合物。本提案的目的是在热烧伤小鼠模型中测试这些化合物，目的如下：1）证明这些化合物中的一种或多种在改善急性烧伤的愈合方面是有效的，2）确定在烧伤损伤后多久可以施用该化合物并且该化合物是有效的，以及3）确定使用该化合物仍然可以显示出多大程度的烧伤伤口的改善。预期的终点是证明在我们的动物模型中，这些化合物中的一种或多种可以在烧伤后立即或不久静脉内或局部施用，并且显示烧伤伤口愈合，与未治疗的动物相比，瘢痕形成和毛发生长损失显著减少。第二阶段SBIR资金将支持肽化合物开发成候选药物，临床前测试和第一阶段人体试验的临床评估。