A research collaboration between Rambam Health Care Campus (Rambam) and the Technion-Israel Institute of Technology (Technion), both in Haifa, Israel, has successfully used genetic engineering to treat cardiac arrhythmias.
Marking a world first, Rambam’s physician scientists have collaborated with Technion researchers to develop a bioengineered receptor that initiates a biological process to regulate the heart’s electrical activity. Theoretically, the patient will be able to activate the receptor by taking a controlled dose of a medication that will act on a specific area of the heart and only when the cardiac arrhythmia occurs. In essence, this receptor serves as a kind of biological defibrillator.
Heart rhythm disturbances, medically referred to as cardiac arrhythmias, occur when the heart beats too fast, too slow, or in an irregular manner. Typically, symptoms can include chest pain, shortness of breath, fatigue, dizziness, or even fainting, and in some cases, they can be life-threatening. Hundreds of thousands of Israelis suffer from this disorder, but arrhythmias represent a very real health concern worldwide. Researchers have been trying to find an effective solution for years.
The research was performed in the laboratory of Professor Lior Gepstein, director of Rambam’s Division of Cardiology and director of Division of Research. Regarding the need for an out-of-the-box solution for cardiac arrhythmias, Gepstein explains, “Medications for treating cardiac arrhythmias are not effective, and can even cause irregularities in other areas of the heart that can be more dangerous than the original arrhythmia. This is the problem we tried to solve.” He further points out that while patients are often given anti-coagulants to prevent the formation of life-threatening blood clots – but anti-coagulants do not deal with the problem itself.
Yehuda Wexler, a doctoral student in Gepstein’s Technion laboratory makes a very complicated process sound quite simple: “Our solution involved genetically engineering and inserting a receptor into a specific area in the heart. From there, the receptor connects to specific cells responsible for the heart’s electrical activity, but remains dormant until the patient feels an arrhythmia. The patient then takes a drug that ‘wakes-up’ the receptor which activates the cells that regulate the electrical activity in the specific area of the arrhythmia, and not the entire heart.”
This method potentially offers a simple and more effective alternative to the drugs and treatments currently available. “Our goal is to determine exactly which cells in the heart must be genetically engineered with the receptor, for example, only cells in a specific cardiac chamber, and to then implant the receptor there. So, for example, a patient who feels atrial fibrillation will take the drug only when the arrhythmia is felt. The drug will effect only the area where the electrical activity needs to be changed—without disrupting the activity of any other cell in the heart or body,” Gepstein continues to explain.
Gepstein’s research team has shown that adjusting the drug dosage can control the receptor and the heart’s electrical activity. They also demonstrated that genetically engineered cells implanted in rats together with the drug (an existing one approved for human use by the American FDA) can control the heart’s electrical activity. Their research has just been published in the prestigious journal, Circulation Research.
Gepstein and colleagues also presented their research at Rambam’s annual Research Day, during which 120 additional studies at various stages of development were presented.
Collaborative research between Rambam, the Technion, and other leading academic institutions has resulted in many world-firsts, and Rambam has deservedly earned the reputation of being a world leader in research and innovation.