A high throughput screening assay for developing therapies to protect from drug and alcohol-induced cardiotoxicity.
Excessive alcohol consumption and many FDA-approved drugs lead to severe cardiotoxicity and heart failure. Cardiotoxicity is one of the leading side effects of medications, accounting for about half of all drug withdrawal. For example, melphalan, a leading chemotherapeutic for treating cancers, severely affects heart cells and causes cardiac abnormalities. Dexrazoxane is one of the only drugs FDA-approved for protecting the heart in those undergoing chemotherapy for cancer and has questionable efficacy. Unfortunately, current models for generating new cardioprotective drugs are insufficient due to lacking physiological relevance to humans and cannot be used in a high-throughput format. Hence, new methods are needed to identify drugs that can help prevent cardiotoxicity for millions requiring lifesaving medicines for various diseases.
Emory researchers have developed a novel method for the high-throughput screening of new drugs to protect against heart damage. The technique uses human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) to reflect phycological conditions more accurately in humans when exposed to alcohol or toxic drugs. Preliminary data using the system demonstrated similar cellular responses as clinically observed cardiac damage in humans when exposed to chemotherapies and alcohol. Furthermore, using the screening platform, the inventors have screened over 2,000 compounds and identified several novel compounds that could be used for cardioprotection.