NOVEL TARGETS FOR CONTROL OF APP EXPRESSION

阿尔茨海默病是一种影响越来越大的重大疾病 占人口的百分比。到目前为止，这种疾病的原因仍然是 未知，使有效疗法的发展复杂化。然而， 继续有证据表明，从该应用程序中提取的Abeta肽 蛋白质在病理学的发展中起着重要的作用。 已经进行了各种研究，试图改变体内的 这种多肽通过翻译后或转录机制。 最近的证据表明，转录后控制可能是另一种 监管APP水平的重要手段。交响乐 制药公司已开发出一项技术，划线水平受到监管。 SYMPHONY制药公司已经开发出一种技术，Scribe(特定于 控制RNA相互作用和结合事件)，以调节蛋白质 转录后水平的表达。交响乐已经使用了脚本来 分离活性化合物作为非AD的适应症。鉴于……的重要性 AD，此第一阶段提案旨在确定目标(范围内的顺元素 应用程序文本)服从于抄写技术。为此，这 提案将系统地绘制整个应用程序的RNA/蛋白质转录本 交互并确定任何交互的功能相关性 被发现了。这些研究的结果将使交响乐与 用于第二阶段药物发现计划的独特靶点。 建议的商业应用：化合物，代表一种新的 作为该计划的结果，确定的行动机制将是 由SYMPHONY开发，作为治疗阿尔茨海默氏症的临床候选药物 疾病。此外，对抄写技术的进一步验证 将应用于其他基因产品和专利检测 将被授权给制药公司进行非中枢神经系统项目。

Alzheimer's disease is a major illness affecting an increasingly larger percentage of the population. As yet, the cause of the disease remains unknown, complicating the development of effective therapeutics. However, evidence continues to implicate the Abeta peptide, derived from the APP protein, as playing an important role in the development of the pathology. Various studies have been carried out in an attempt to alter the levels of this peptide through post-translational or transcriptional mechanisms. Recent evidence suggests that post-transcriptional control may be another important means by which APP levels are regulated. Symphony Pharmaceuticals has developed a technology, SCRIBE levels are regulated. Symphony Pharmaceuticals has developed a technology, SCRIBE (Specific Control of RNA Interactions and Binding Events), to regulate protein expression at the post-transcriptional level. Symphony has used SCRIBE to isolate active compounds for a non-AD indication. Given the importance of AD, this Phase I proposal seeks to identify targets (cis-elements within the APP transcript) amenable to the SCRIBE technology. To that end, this proposal will systematically map the entire APP transcript for RNA/protein interactions and determine the functional relevance of any interactions discovered. The results from these studies will position Symphony with unique targets for use in a Phase II drug discovery program. PROPOSED COMMERCIAL APPLICATION: Compounds, representing a novel mechanism of action, identified as a result of this program will be developed by Symphony as clinical candidates for treatment of Alzheimer's disease. In addition, the further validation of the SCRIBE technology will have applications for other gene products and the proprietary assays will be licensed to drug companies for non-CNS programs.