Brain disorders such as autism, major depressive disorder and Alzheimer’s disease are among the greatest medical challenges of our era. Many drugs targeting the central nervous system (CNS) have been developed to modulate G protein-coupled receptors, ion channels or transporters with mitigated success. There remains a shortage of disease-relevant targets that can be harnessed for drug discovery to treat the onset and progression of brain disorders/diseases. This project focuses on RNA-binding proteins as untapped therapeutic targets because of their important role in the brain. Members of the RNA-binding protein family provide powerful post-transcriptional control over cellular phenotype by regulating up to 30% of the variation of the cellular proteome. Recent human genetic studies further implicate RNA-binding proteins in many neurodevelopmental, neuropsychiatric disorders and neurodegenerative diseases.
The team will develop a first-in-kind sensitive, adaptable, and validated HTS platform called ShARP for Screenable Assays for RNA-bindingProteins. This platform is based on the use of specific untranslated regions (UTRs) that are targeted by RNA-binding proteins to modulate recruitment of mRNA to ribosomes during protein synthesis. The principal reporter readout will be luminescence and is thus compatible with existing technologies and instrumentation. There are presently no effective tools to explore the usefulness of RNA-binding proteins for drug development. This platform will have major benefits for the biopharmaceutical industry as it will promote new drug target identification, aid with the drug discovery/screening process and promote optimization and validation of promising first-in-class CNS-relevant drugs to treat challenging brain diseases.
Content from CQDM: https://www.cqdm.org/en/projects-portfolio/project/67