Researchers at the University of Rochester Medical Center are leading an international study testing a new drug for patients with an inherited heart rhythm disorder called Long QT syndrome 3 (LQT3). The drug is designed to treat a specific glitch in the heart’s electrical system that’s caused by a genetic mutation found in patients with this rare disorder.
The phase III clinical trial puts precision medicine – a treatment approach that takes into account individual variability in genes and other characteristics – to the test in the field of cardiology. Precision medicine is most often discussed in relation to the treatment of cancer, but efforts are underway to apply it in many more areas of medicine. Earlier this year, President Obama announced plans for a Precision Medicine initiative designed to speed up these efforts.
“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.”
Long QT syndrome is one of the leading causes of sudden cardiac death in adults and children. Patients are at high risk of irregular heart rhythms called arrhythmias that, if not corrected, can lead to fainting spells and death. Researchers have discovered more than a dozen genes associated with Long QT syndrome, including the gene that leads to LQT3. A mutation within this gene alters the electrical switches in the heart that help maintain a regular heartbeat.
Currently, the only treatment for LQT3 is beta blockers, which cause the heart to beat more slowly and with less force. But, it is not clear how well they protect patients from the abnormally rapid heart rhythms that can occur at any time and without warning.
“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.”
Rosero, who treats LQT3 patients from all over the country, says that there are electrical switches throughout our body that play a key role in many activities of daily living like eating, sleeping, walking and brain activity. The new drug, called GS-6615, only targets the dysfunctional electrical switches in the heart: the hope is that sparing all of the other electrical switches in the body will minimize side effects.
Zareba is the principal investigator of the trial, which is sponsored by Gilead Sciences, Inc., the developer of GS-6615. It will take place at five to 10 sites in the U.S. and Europe. Rosero is heading trial recruitment at the University of Rochester and says that three patients are already enrolled.
The University of Rochester Medical Center has a long history in the research and treatment of arrhythmias and Long QT syndrome. In 1979, Arthur J. Moss, M.D., the Bradford C. Berk, M.D., Ph.D. Distinguished Professor in the Department of Medicine, launched an international registry for families with Long QT – one of the first registries for any inherited disease in the world. By following generations of patients with this disorder, Moss, Zareba and scientists around the world have used the registry to track down more than 500 genetic mutations involving 13 genes that cause various versions of Long QT. Without this work, the development of drugs like GS-6615 would not have been possible.
If GS-6615 is effective in treating LQT3, Rosero says that it may be considered for the treatment of other, more common types of arrhythmias like atrial fibrillation. Zareba adds that no new anti-arrhythmic drugs have been approved in the last 25 years and newer, safer options are greatly needed.
Rosero is a paid consultant to Gilead in the area of precision medicine.