Serious drug-induced cardiac side effect accurately detected and scored by LIMR researcher and colleagues
TdP is a life-threatening form of ventricular tachycardia that often occurs as a result of the heart taking longer to recharge between beats, or QT prolongation. Clinicians have known that certain approved and experimental medications can inadvertently cause QT prolongation. The risk is so great, in fact, that the U.S. Food and Drug Administration (FDA) now requires all drug candidates in development to be tested to ensure they don’t cause QT prolongation before entering into clinical use. But testing in patients isn’t always possible, so the FDA has called for preclinical testing methods.
LIMR professor Gan-Xin Yan, MD, PhD — along with colleagues at the FDA, Janssen Pharmaceuticals, GlaxoSmithKline and Peking University — demonstrated in a recently published, blinded study that the Normalized TdP Score System they developed successfully predicted the proarrhythmic risk of 34 medications.
To complete their study, the team used Dr. Yan’s arterially perfused ventricular wedge preparation (‘wedge prep’ for short), an invention previously shown to accurately record all electrical signals in the heart, even in its innermost layers. Previously, scientists could record only the signals sensed on the outside of the heart.
In the current study, researchers used Dr. Yan’s wedge prep to detect signals on the inside of animal hearts, each of which had been treated with one of the 34 studied medications. They then assigned scores to those drugs, thus enabling an accurate risk assessment of a medication’s ability to induce TdP.
“There has long been a need to reliably predict TdP risk among drug candidates,” said Dr. Yan. “We’ve now shown that using our normalized TdP score by the wedge prep assay can enable pharmaceutical researchers to readily determine drug-induced TdP risk among their compounds. We think this assay will turn out to be a best-practice preclinical drug-safety solution for pharmaceutical development and may eventually reduce the need for human QT studies.”
The study, “Utility of normalized TdP score system in drug proarrhythmic potential assessment: a blinded in vitro study of CiPA drugs” was published in Clinical Pharmacology and Therapeutics.
About Lankenau Institute for Medical Research
Lankenau Institute for Medical Research (LIMR) is a nonprofit biomedical research institute located on the campus of Lankenau Medical Center and is part of Main Line Health. Founded in 1927, LIMR's mission is to improve human health and well-being. Using its ACAPRENEURIALTM model that integrates academic and entrepreneurial approaches, faculty and staff are devoted to advancing innovative new strategies to address formidable medical challenges including cancer, cardiovascular disease, tissue regeneration, gastrointestinal disorders and autoimmune diseases such as diabetes and arthritis. LIMR's principal investigators conduct basic, preclinical and clinical research, using their findings to explore ways to improve disease detection, diagnosis, treatment and prevention. They are committed to extending the boundaries of human health through technology transfer and training of the next generation of scientists and physicians.