NOVEL TARGETS FOR CONTROL OF APP EXPRESSION

阿尔茨海默病是一种影响越来越大的主要疾病

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.