Andrew R. Marks, M.D., FAHAMarks develops drugs to improve stents, angioplasty and prevent sudden death
The arterial stent has been a major medical advance for treating blockages. However, 10 to 20 percent of patients experience restenosis, or a re-blocking of the artery caused by the cells from the blood vessel growing on the stent. Andrew R. Marks, M.D., FAHA, chairman and professor of physiology and cellular biophysics at Columbia University Medical Center in New York City, addressed this complication by coating stents with drugs. The restenosis rate for coated stents is currently less than 10 percent.
Rapamycin is one of two drugs used to coat stents. It is an immunosuppresent, which inhibits blood vessel cells from forming. Rapamycin was discovered in a soil sample from Easter Island, and it was initially developed as an antifungal agent because of its ability to inhibit the growth of yeast. It also had a powerful side effect -- immunosuppresent activity in mammals -- so it’s development as an antibiotic was stopped. But it was just the thing Marks needed to enhance stent therapy.
Marks is testing the drug for other advances as well. “We have shown that an rapamycin inhibits vascular smooth muscle cell migration and restenosis after angioplasty,” he said. He has also initiated studies to determine whether it can inhibit the progression of accelerated arteriopathy after cardiac transplantation.
Since 1986, Marks has held American Heart Association grant awards for work on calcium channels that is indirectly connected to his work on stent restenosis.
“Leaky calcium channels can cause arrhythmia in people with congestive heart failure and those who have an inherited disorder that is exacerbated by exercise, which can result in sudden death,” he said. Building upon 15 years of research, Marks recently developed and tested a drug that completely prevented sudden death from arrhythmia in mice with the same heart defect as people with heart failure.
Every mouse given the drug thrived and never developed an arrhythmia, while eight out of nine untreated mice died of cardiac arrest.
“The drug will be an incredible advance if it works in patients,” Marks said. "It represents the beginning of an era when drugs will directly fix the molecular defects in heart failure. While our drug is one of the first molecular-based therapies for heart failure and arrhythmias, it won’t be the last.
“AHA should take credit for this work. I have always been supported by AHA, and that support was instrumental in my development as a scientist.”