DerG (a new immunomodulator) Treatment of Viral Encepha*

DerG（一种新型免疫调节剂）治疗病毒性脑病*

• 批准号: 6723673
• 负责人: KENNETH S ROSENTHAL
• 金额: $ 32.94万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6723673
• 关键词: Alphavirus; analog; antiviral agents; bioassay; cooperative study; drug design /synthesis /production; drug screening /evaluation; herpes simplex virus 1; herpes simplex virus 2; immunomodulators; infectious encephalitis; laboratory mouse; pharmacokinetics; technology /technique development; tissue /cell culture

DESCRIPTION (provided by applicant): The ultimate goal of this program is to develop a prophylactic or therapeutic agent (derG) for treatment of medically important viral and other infections for which there may not be treatment or the treatment is too toxic. DerG was identified as a new immunostimulatory peptide as a result of work on L.E.A.P.S.TM vaccine technology. The derG peptide is based on sequence from the beta chain of the MHC II molecule and is an altered peptide ligand of the CD4 molecule. Preliminary studies in different laboratories indicate that derG can induce protection against parasitic malarial sporozoite and herpes simplex virus challenge and act as an adjuvant for tumor vaccine therapy. Administration of derG within 3 days (or less) or up to 4 weeks in advance of infectious challenge elicited protection against HSV challenge. The proposed investigation will extend our studies of derG on HSV and determine by using mouse models whether derG protects against viral encephalitis by HSV and an arbovirus, S.A. AR86 sindbis-Iike alphavirus. Our specific aims are to: 1) establish the efficacy of derG against these viruses; 2) develop in vitro assays for derG activity to allow screening of analogues, other drugs and to maximize potential for the following aims; 3) determine the mechanism of action of derG; 4) design and prepare for evaluation derG analogues in vitro and in HSV challenge models and initiate procedures required to pursue FDA approval of derG for human therapy. This project is part of a continued collaboration between an academician and CEL-SCI Inc., a biotechnology-vaccine development company. CEL-SCI is committed to provide support including technological development, quality control, scale up to GMP level development, access to preclinical development, methods for toxicological and pharmacological testing, clinical testing and data management resources. Successful development of derG may provide a broad spectrum, immunoenhancing prophylactic and therapeutic treatment that can be provided in lieu of, or to enhance vaccination prior to travel or assignment to a region of high risk for exposure to infectious or bioterror agents upon short notice.

描述（由申请人提供）：该计划的最终目标是开发一种预防或治疗剂（derG），用于治疗医学上重要的病毒和其他感染，这些感染可能无法治疗或治疗毒性太大。由于 L.E.A.P.S.TM 疫苗技术的研究成果，DerG 被确定为一种新的免疫刺激肽。 derG 肽基于 MHC II 分子 β 链的序列，是 CD4 分子的改变的肽配体。不同实验室的初步研究表明，derG 可以诱导针对寄生疟疾子孢子和单纯疱疹病毒攻击的保护，并可作为肿瘤疫苗治疗的佐剂。在感染攻击前 3 天（或更短时间）或最多 4 周内施用 derG 可引发针对 HSV 攻击的保护作用。拟议的研究将扩展我们对 derG 对 HSV 的研究，并通过使用小鼠模型确定 derG 是否可以预防 HSV 和虫媒病毒 S.A. AR86 辛德比斯样甲病毒引起的病毒性脑炎。我们的具体目标是：1）确定 derG 针对这些病毒的功效； 2) 开发 derG 活性的体外测定法，以筛选类似物、其他药物，并最大限度地发挥实现以下目标的潜力； 3）确定derG的作用机制； 4) 设计并准备在体外和 HSV 攻击模型中评估 derG 类似物，并启动寻求 FDA 批准 derG 用于人类治疗所需的程序。该项目是一位院士与生物技术疫苗开发公司 CEL-SCI Inc. 持续合作的一部分。 CEL-SCI 致力于提供包括技术开发、质量控制、扩大到 GMP 水平开发、获得临床前开发、毒理学和药理测试方法、临床测试和数据管理资源等支持。 derG 的成功开发可以提供广谱、免疫增强的预防和治疗性治疗，可以在旅行或分配到接触传染性或生物恐怖剂的高风险地区之前代替或加强疫苗接种。