PFI-TT: Automated Platform for Drug Testing in Human Heart Cells Using Light

点击翻译按钮获取中文摘要

The broader impact/commercial potential of this PFI project on the economy and public health in the United States will be achieved by providing drug and stem-cell researchers and developers with a superior yet low-cost technology for detection of adverse effects on the heart to deliver cheaper, more effective, and safer drug treatments. Drug development is expensive ($2.6 billion per drug) and a high-risk process, where inadequate assessment of failures prior to clinical trials and market approval can result in loss of human life and come at great financial losses to investors, termination of employees, and potential outsourcing to developing countries. The proposed technology will improve failure prediction during early preclinical testing, where future adoption of the commercialized product will reduce drug development opportunity costs. It will also enable the pursuit of more challenging projects, including personalized therapies and therapies tailored for specific patient populations, e.g. considering sex, race or other characteristics when testing a new drug treatment. The female team behind the technology is committed to the successful establishment and growth of a company with a goal to help improve diversity in the STEM-related startup field, and serve as allies and role models for future STEM entrepreneurs from all backgrounds.The proposed project will develop technology for basic and translational work in cardiac electrophysiology. It will empower mechanistic studies of potentially lethal heart arrhythmias by yielding high-content high-quality information about cardiac electrical dysfunction, relevant for the discovery of new antiarrhythmic therapies. The integration of optogenetic methods and optical imaging offers high-throughput functional assessment and enables personalized solutions in drug screening. The unmet needs and advantages offered by the technology include compatibility with human stem-cell-derived cardiomyocytes and tissue constructs, provision of controlled pacing conditions while gathering multiparameter spatio-temporal information for better predictions of drug attrition, and low-cost. The following challenges in the translation to commercial applications are addressed: 1) determine the optimal optical configuration for a stand-alone prototype that is low-cost, compact, and customizable with user-friendly software; 2) establish the workflow for scientifically valid (double-blinded and controlled) assay designs using the system; 3) identify key measurements (biomarkers) and algorithms to predict how in vitro data translates to in vivo clinical outcomes (endpoints). This will result in a free-standing prototype that can be easily integrated into established workflows, an expanded library of compounds tested in a blinded, controlled study, and arrhythmia prediction software that utilizes measured data to stratify cardiotoxicity risk.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.