Expansion of an efficient drug repurposing platform for rare genetic diseases.

DESCRIPTION provided by applicant There are thousands of rare genetic diseases that have no approved treatment Recursion Pharmaceuticals has developed a drug discovery platform that seeks to re purpose known drugs for the treatment of such diseases The platform consists of high content immunofluorescent image analysis and transcellular resistance measurements These measurements evaluated using machine learning algorithms to identify relevant and on target changes induced by both RNAi and various chemicals These assays can be simultaneously performed on thousands of rare genetic disease models In this grant we specifically propose to Model genetic diseases in multiple human cell types using RNAi technology Identify and prioritize of these disease models with the most compelling phenotypic changes according to multi parametric quantification Utilize these disease models as the basis of chemical suppressor screens of thousands of known drug candidates Validate the best drug disease combinations using an orthogonal genetic manipulation technique in human cells Study the best five to ten validated drug disease combinations in relevant animal models The proposed study would have significant societal and commercial implications PUBLIC HEALTH RELEVANCE There are thousands of rare genetic diseases that together affect millions of Americans We will use chemical suppressor screens of known drugs based on structural and functional changes in cellular disease models to identify potential therapeutics for treatment of these diseases