Promise of New Treatments for Pulmonary Arterial Hypertension
Discoveries in the lab of Youyang Zhao, PhD, at Stanley Manne Children’s Research Institute at Lurie Children’s, hold promise of new treatments for patients suffering from pulmonary arterial hypertension (PAH), a severe lung disease with three-year survival rate of 50 percent. Based on his findings, new drugs can be developed to treat the devastating disease, which could save lives.
Patients with PAH have high blood pressure in the arteries of their lungs. This is caused by progressively thickening walls of the lung arteries, a process called “vascular remodeling,” which interferes with the smooth flow of blood from the heart, ultimately resulting in heart damage. In severe cases, the pulmonary arteries become completely blocked, leading to right-sided heart failure and death.
“Today we do not have treatments for pulmonary arterial hypertension that target the mechanisms behind disease development,” says Dr. Zhao. “Now we are a step closer to such treatments. Our lab has shown that we can inhibit vascular remodeling and improve survival in mouse and rat models of the disease.”
Dr. Zhao and colleagues have created a unique genetically modified mouse model of PAH that is the first to closely mimic how the disease progresses in patients. They also were the first to establish that in PAH, diminished expression of a gene called PHD2 in the artery wall activates increased expression of another gene, HIF-2α, which promotes vascular remodeling and blocked arteries in the lungs. When the team suppressed HIF-2α activity with a drug compound, they observed that the mice no longer developed thicker arterial walls. The disease was stopped in its tracks.
Dr. Zhao and his team’s findings were recently published in the American Journal of Respiratory Critical Care Medicine. According to study lead author Zhiyu Dai, PhD, a research assistant professor in the Zhao lab, a clinical trial of the new drug will launch later this year.
“These results serve as a foundation for developing new drugs to safely and effectively prevent, stop, and even reverse vascular remodeling in patients,” says Dr. Zhao. “Our mouse model can also be used for developing a gene therapy approach to treating pulmonary arterial hypertension.”
Dr. Zhao’s research is supported by funding from the National Institutes of Health. He is the William G. Swartchild, Jr. Distinguished Research Professor and Director of the Program for Lung and Vascular Biology at the Manne Research Institute. Dr. Zhao is also a Professor of Pediatrics, Medicine and Pharmacology at Northwestern University Feinberg School of Medicine.