A team of scientists at the University of Rochester Medical Center is spearheading a global drug study for patients diagnosed with Long QT Syndrome, a hereditary cardiac rhythm disorder. The drug, GS-6615, is formulated to work on a specific abnormality in the heart’s conductive system, caused by a genetic aberration in patients with this disease.
The Phase III study makes use of precision medicine, an emerging approach to understanding and treating disease that takes into consideration patients’ individual genetics and characteristics. While it is most commonly applied in the study of cancer, it is steadily gaining popularity in a variety of other fields, such as in cardiology.
“This study is unique because it is one of the few examples of the use of precision or personalized medicine in heart disease,” said Wojciech Zareba, M.D., Ph.D., professor of Medicine and director of the Heart Research Follow-up Program at the University of Rochester Medical Center. “Our goal is to deliver the right drug, at the right dose, to the right patient. We’re hopeful that this study will help us achieve that and improve the survival and quality of life of patients with LQT3.”
This cardiac disease ranks as one of the primary causes of sudden cardiac death in both adult and pediatric patients, as the associated arrhythmias, if left unmanaged, can lead to recurrent instances of syncope. Previous studies have identified over a dozen genes linked to Long QT Syndrome, along with a rare gene that can put an individual at risk for LQT3. This specific genetic mutation can hinder the heart’s ability to maintain a regular heartbeat. Today, the only available treatment for LQT3 are beta blockers, which reduce heart rate and contractility, but do not specifically address spontaneously occurring arrhythmias.
“In the past we used one drug to treat a disease, but now we are narrowing diseases by gene mutations and customizing drugs to target distinct mutations and minimize side effects,” noted Spencer Z. Rosero, M.D., associate professor of Medicine and director of the Hereditary Arrhythmias Clinic at UR Medicine’s Strong Memorial Hospital. “This approach is much more focused and should lead to better outcomes for patients.”
According to Rosero, the human body has a map of electrical switches that innervate various activities, and can be specifically targeted. GS-6615 has the specificity to act only on the heart’s electrical switches, without causing any systemic side effects.
Lead investigator Zareba is conducting the trial with support form Gilead Science, Inc. It will be offered across 5 to 10 sites across the US and Europe. Rosero will be leading trial recruitment at the University of Rochester, wherein 3 patients have already been enrolled.
The University of Rochester Medical Center has long since been studying cardiac arrhythmias and Long QT syndrome, with one of its professors of medicine, Dr. Arthur J. Moss, launching an international registry for families with Long QT – one of the first databases of an inherited disease. Through this registry, present and future scientists around the globe can trace over 500 genetic mutations of 13 genes previously linked to Long QT. Without Dr. Moss’ pioneering work, many of what are known and available today would not exist.