Mount Sinai scientists and clinicians are making notable advances in the study and treatment of heart failure, a common condition that occurs when the heart becomes too weak to pump and circulate enough blood through the body. Diseases that damage the heart—such as coronary artery disease, high blood pressure, and diabetes—can lead to heart failure, which develops over time as the heart’s pumping action grows weaker. It impacts an estimated 5 million adults and children in this country.
In a recent study, investigators from the Icahn School of Medicine at Mount Sinai found that a powerful drug candidate, a small molecule known as N106, was able to improve the pumping ability of heart muscle cells that had been damaged by heart failure. The molecule was tested in human heart cells and animals, and the study’s findings were published online on Friday, June 12, in Nature Communications. The study was a collaborative effort between Mount Sinai’s Cardiovascular Research Center and the Experimental Therapeutics Institute.
“This first-in-class small molecule targets a known cellular pathway, improves heart failure cell abnormalities, and may provide an essential future treatment for these patients,” says Roger J. Hajjar, MD, Director of the Cardiovascular Research Center, and the Arthur and Janet C. Ross Professor of Medicine, who led the study. “Our research team will drive the development of this new class of agents to enable the launch of the first clinical trials to test this promising medicine in heart failure patients.”
Treatment with N106 appeared to increase heart muscle contraction, which resulted in the improved ability to pump blood. Specifically, N106 may counter heart failure by directly docking to and activating an enzyme, E1 ligase, which turns up the function of another, SERCA2a (Sarcoplasmic Reticulum Calcium ATPase). SERCA2a is a critical protein responsible for the proper flow of charged particles, such as calcium, in and out of heart muscle cells, which is needed to drive muscle contraction. Abnormal calcium cycling and decreased expression of SERCA2a in heart muscle cells is a major hallmark of heart failure, forcing the heart to work harder and grow larger, even as it weakens. This research builds upon Dr. Hajjar’s previous work in targeting dysregulated calcium cycling proteins for the treatment of heart failure.
“Our new discovery of the promising compound N106 is a very exciting milestone for greater precision and targeted therapies for this debilitating condition,” says Robert J. DeVita, PhD, Director of Medicinal Chemistry Core, Experimental Therapeutics Institute. “There is a critical need for novel targets and treatment strategies for heart failure.”
A New Way to Monitor Heart Failure Patients
In mild cases, heart failure can be treated with lifestyle modification or daily medication. In severe cases, patients may need surgical intervention for survival: mechanical support, such as a left ventricular assist device, or a donor heart transplant. The cost of heart failure care is an estimated $32 billion in the United States each year.
Among key symptoms for heart failure are shortness of breath and tiredness, the result of fluid build-up in the lungs, ankles, feet, legs, and other areas of the body. Frequently, these conditions lead to hospitalization, which is what 54-year-old Julie Bailey faced in March, when fluid retention in her lungs left her unable to walk. Ms. Bailey, who was living with heart failure for 24 years, had been hospitalized twice in the last two years.
Raymond Bietry, MD, Assistant Professor of Medicine (Cardiology), Icahn School of Medicine at Mount Sinai, had a solution: in addition to diet changes and tobacco cessation, he recommended a new heart failure monitoring device that would help to detect symptoms earlier, a strategy aimed at reducing hospital admissions and improving quality of life.
Ms. Bailey recently became the first patient at Mount Sinai to receive the dime-sized CardioMEMS™ sensor, a device—which requires no batteries or leads—that is placed directly inside the heart during a minimally invasive procedure. The device monitors for increases in pulmonary artery pressures, early indicators of worsening heart failure. Patients transmit their daily pressure readings to their medical team, who have the ability to provide individualized and real-time care when there are abnormalities.
Ms. Bailey recalls that the first time she transmitted the data, a member of Dr. Bietry’s staff called to inquire what she had eaten that day, suspecting that her answer would likely help explain the increased pressures they had noted. After revealing she had eaten a Greek salad with salty olives and cheese, she was reminded to select foods with less sodium.
Ms. Bailey is reassured by the greater levelof communication and personalized care. “My doctors can monitor me wherever I am,” she says. “I’m having a moment of success.”