Novel Methodology for Identification of Senolytics that Reduce Age-related Disease and Dysfunction

DESCRIPTION provided by applicant Chronic diseases of aging account for a significant proportion of healthcare spending and result in a painful and limiting existence for many tens of millions of Americans and hundreds of millions of people around the world Recursion Pharmaceuticals has developed a drug discovery platform that re purposes known drugs for the treatment of such diseases The platform consists of high content fluorescent image analysis using machine learning algorithms to identify relevant and on target changes induced in human cells in which diseases and treatments have been modeled This system has been adapted to screen for drugs which may preferentially destroy senescent cells as this may result in improved tissue function and decreases in pathology and mortality related to aging In this SBIR fast track proposal we will PHASE I Identify a morphological profile of senescence in a variety of human cell types Progression to Phase II will depend on our ability to demonstrate the power of our morphological approach to identify senescent cells independent of any known senescent markers PHASE II Identify known drugs which preferentially destroy senescent cells without affecting healthy cells as identified by morphometric means Evaluate the efficacy of identified senolytic agents in a variety of tissue function and health span models in mice Evaluate the effect of identified senolytic agents in a murine model of age associated cardiovascular disease Recursion Pharmaceuticals has the experience tools and drive to execute this Phase I Phase II Fast track SBIR proposal and to accelerate commercial development of any compounds we identify as a result PUBLIC HEALTH RELEVANCE Chronic diseases of aging affect a significant proportion of Americans Cellular senescence a useful biological program which prevents replication of cells exposed to various stresses that may be at risk of initiating tumors has long term deleterious inflammatory effects We will combine biological imaging and computational approaches to identify complex morphological profiles associated with senescence to identify senescence killing effects of known drugs and to evaluate any hits in relevant models of aging