Personalized Medicine Arrives At Mount Sinai Medical Center

Clinical demonstration project offers genetic testing to help doctors predict if their patient will benefit from antiplatelet drug clopidrogel

The Charles R. Bronfman Institute for Personalized Medicine and Mount Sinai’s Cardiac Catheterization Laboratory launch a clinical demonstration project providing advanced genetic testing to improve the antiplatelet therapy of heart disease patients who have intracoronary stents placed in a procedure called percutaneous coronary intervention or PCI. By offering a genetic test that helps to predict which patients will not receive a benefit from the platelet inhibitor Plavix, prescribed to prevent clots from forming around the stent, doctors at Mount Sinai Heart now have the option to select proactively the most effective drug for individualized antiplatelet treatment.

"As a pioneer in adopting genetic testing for clinical care, we are committed to deliver groundbreaking advances in personalized medicine to providers and patients" says Erwin Bottinger, MD, Director, Charles R. Bronfman Institute for Personalized Medicine. "The Institute for Personalized Medicine is privileged to partner with Mount Sinai’s world-renowned team of interventional cardiologists, led by Samin Sharma, MD, and state-of-the-art genetic testing laboratory services led by Robert Desnick, MD, PhD, Chair, Department of Genetics and Genomic Sciences, and David Zhang, MD, PhD, Director, Molecular Pathology to bring the promises of cardiac pharmacogenomics from bench to bedside.

Several thousand heart disease patients undergo PCI procedures with stent placements at the Cardiac Catheterization Service of Mount Sinai Heart each year. Use of the antiplatelet agent clopidogrel (Plavix) with aspirin has substantially reduced the risk of recurrent ischemia, stent thrombosis, and death in Patients with PCI and stents. However, studies found that at least one in 40 patients does not get the protective antiplatelet effect of Plavix and in one third the drug may only be partially effective because these individuals have non-functioning versions of the CYP2C19 gene, which makes the cytochrome P450 enzyme that is required to produce the activate drug metabolite.

With the clinical demonstration project, Mount Sinai is among the first medical centers where genetic testing to identify patients who carry non-functioning versions of the CYP2C19 gene can be performed and reported between patient’s arrival at the catheterization laboratory and release from the hospital. This allows Dr. Sharma and his colleagues to identify the majority of patients with stent placements who respond to Plavix and to select alternative treatments, such as Prasugrel, prior to discharge for a minority of patients who do not get any benefit form Plavix because they carry non-functioning CYP2C19 gene versions.

According to Dr. Bottinger, development and clinical validation of assays for a broad range of other pharmacogenomic and predictive genetic variants is ongoing in Mount Sinai’s Genetic Testing and Molecular Pathology Laboratories with support from the Institute for Personalized Medicine. "We are completing the required clinical validation of microarray assays to determine the genetic variation of more than 200 genes involved in drug responses with a single comprehensive test " says Dr. Zhang, who is leading Molecular Pathology at the Center for Clinical Laboratories.

While its research and clinical genetics teams are developing and validating these assays, the Mount Sinai Personalized Medicine team is evaluating scientific reports with clinical leaders to prioritize the most promising, actionable genetic tests for clinical translation, and to educate physicians and the patients. In parallel with patient and physician education in genomics, the Mount Sinai’s Information Technology Department and the Institute for Personalized Medicine have joined efforts to create informatics solutions to make personal genetic data accessible for authorized physicians, and in the future also patients, safely and confidentially through its electronic medical record system. "Mount Sinai is preparing to deliver personalized medicine to its clinicians and patients in a big way" says Dr. Bottinger.