A humble plant could offer hope for people at risk of pulmonary hypertension.
Researchers at the University of Pennsylvania (Penn) and the University of Florida in the United States have identified a drug that can be used to treat those suffering from the condition, for which few therapy options exist. The medicine is grown in the leaves of plants from Penn’s greenhouse. The team says that in patients with pulmonary hypertension, the arteries of the lungs become constricted, which increases the workload on right side of the heart to pump blood through the lungs. Over time, the right chamber of the heart, which usually is small, becomes enlarged and dysfunctional. Currently, the most successful drugs for the disease cost tens of thousands of dollars.
That could change according to the researchers on the study, for whom the senior author of the study was Henry Daniell, professor of biochemistry and pathology and director of translational research at Penn’s School of Dental Medicine. Fellow Penn Dental Medicine authors included postdoctoral associate Kwang Chul-Kwon and research assistants Shina Lin and Guiying Jin. The Penn team collaborated with researchers from the University of Florida, including Vinayak Shenoy, an assistant research scientist in the College of Pharmacy Department of Pharmacodynamics; co-senior author Mohan Raizada, a distinguished professor of physiology and functional genomics in the Evelyn F. and William L. McKnight Brain Institute; and Michael Katovich, a professor in the College of Pharmacy.
Vinavak Shenoy said: “Pulmonary hypertension is relatively a rare disease. It’s been neglected by the industry so there aren’t many drugs out there. “The first drug for pulmonary hypertension was approved in 1995, although the disease was known since the early 1900s.” Mohan Raizada said that blood pressure is regulated by a hormonal system called the renin-angiotensin system. Too much of a key hormone in this system, angiotensin II, can raise blood pressure. However, angiotensin II is balanced by two other hormones , ACE 2 and Ang-(1-7), that maintain normal cardiopulmonary pressure, according to previous research. The research has shown that increasing the amount of these hormones in the body prevents pulmonary hypertension. Because the hormones are already found in the human body, they had little concern about potential side effects.
Mohan Raizad said: “All of the drugs on the market so far for hypertension and cardiovascular diseases are based on inhibiting angiotensin II and aren’t very effective. “Many years ago, we began to question why the prevalence of hypertension and cardiopulmonary diseases does not decrease when you inhibit angiotensin II. Instead, we thought we should be targeting the hormones that balance angiotensin II.” Prof Daniell said: “The proteins we were dealing with are very large and unstable, only lasting a few minutes in the bloodstream when given as an injection, “We needed to find a way to stabilise the proteins to increase their lifespan in the bloodstream and make sure it was working the way we wanted it to.”
When patients are treated with other medications, they typically see only a slight improvement — about a 10% reduction in pulmonary pressure. After the rats with established pulmonary hypertension had been treated with the medication for two weeks, their pulmonary pressure was reduced by 20%. After four weeks of using the plant-delivered medication to treat a group of 8-10 rats with pulmonary hypertension, the researchers found that the medication reduced pulmonary pressure by 32%. Vinavak Shenony said that, although pulmonary hypertension causes vessels in the lungs to constrict, patients actually die from heart failure. However, the drug improved function on the right side of the heart, potentially avoiding heart failure in patients.
The researchers now hope to test the drug in clinical trials and Mohan Raizada said: “The bottom line is that we have been able to find a revolutionary way to deliver a therapy through oral delivery for a disease which is in critical need for an immediate innovative therapy.”
The study was funded by the National Heart Lung and Blood Institute, National Institutes of Health and American Heart Association.