AN IN VITRO HIGH THROUGHPUT STEM CELL HEMOTOXICITY ASSAY

Present hemotoxicity testing during drug development has a low predictability level. In contrast, the in vitro hematopoietic stem and progenitor cell colony-forming assays (CFA) provide validated and highly predictive procedures which can be extrapolated to other proliferating cell systems and are capable of improving the efficacy and safety for new drug development. Here, we will develop a modified read-out CFA procedure that further improves the sensitivity and transforms the test into a robust, non-subjective, easy-to-use, high throughput and cost-effective hemotoxicity assay by using either a fluorescence or luminescence signal detection system capable of measuring both cell proliferation and inhibition/apoptosis. The new assay could be incorporated into lead optimization and preclinical drug development as well as clinical trial patient monitoring. We will use the assay in validation studies aimed at testing a large variety of different compounds. Incorporating the assay into drug development programs will reduce the number of animals used during preclinical studies, and could help reduce the overall drug attrition rate. The assay would also be used in other clinically-relevant areas such as quality control and monitoring of growth potential during stem cell transplantation and in neutraceutical and environmental agent testing. PROPOSED COMMERCIAL APPLICATIONS: Development of a predictive, high throughput, cost-effective in vitro hematopoietic stem cell assay would: (1) reduce the number of animals used during preclinical studies; (2) reduce the attrition rate during drug development; (3) reduce toxicity and improve efficacy and safety for the patient; (4) allow better quality control and monitoring of stem cell transplantation procedures; (5) allow HemoGenix to provide better cost-effective service for its clients. The assay therefore has multiple commercial applications.