Nav: Home

Drug identified that could reverse pulmonary arterial hypertension

August 08, 2018

Scientists at Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago took a major step toward developing a new treatment for pulmonary arterial hypertension (PAH), a severe lung disease with a five-year survival rate of 50 percent. They identified a drug with a positive safety profile that inhibits a gene called HIF-2α, which they discovered earlier promotes the progressive thickening of the lung artery walls - a key feature of PAH called "vascular remodeling," which leads to right-sided heart failure, the main cause of death in PAH patients. Recently, they demonstrated in three clinically-relevant animal models that inhibiting HIF-2α with a compound results in reversal of established PAH, suppression of vascular remodeling and right heart failure, and increased survival. These findings were published in the American Journal of Respiratory Critical Care Medicine.

"We are thrilled to reach this critical stage in developing the first drug for pulmonary arterial hypertension that targets the mechanisms behind disease development," says lead author Zhiyu Dai, PhD, from the Manne Research Institute at Lurie Children's, who also is a Research Assistant Professor of Pediatrics at Northwestern University Feinberg School of Medicine. "We plan to complete preclinical testing of the new drug by the end of 2018 and launch a clinical trial in 2019."

In PAH, vascular remodeling causes high blood pressure in the lung arteries, interferes with the smooth flow of blood from the heart and ultimately results in right heart damage. In severe cases, the pulmonary arteries become completely blocked, leading to right heart failure and death. Currently, there is no effective therapy to reverse vascular remodeling and inhibit right heart failure in PAH. Available treatments mainly target vasoconstriction, or contraction of the lung arteries, achieving only modest improvements in PAH morbidity and mortality.

"It is exciting to see our research progressing from the bench to the bedside," says senior author and program director Youyang Zhao, PhD, from the Manne Research Institute at Lurie Children's and Professor of Pediatrics, Medicine and Pharmacology at Northwestern University Feinberg School of Medicine. "We started with creating a unique genetically modified mouse model that is the first to mimic how pulmonary arterial hypertension develops in patients. This helped us establish the potentially therapeutic benefits of inhibiting HIF-2α and the feasibility of doing this with a compound. Now we have a promising drug that we know is safe to test in a clinical trial. We are hopeful that it can reverse vascular remodeling in patients with this devastating disease and ultimately save lives."
-end-
This research is supported in part by grants from the National Institutes of Health.

Dr. Zhao is the William G. Swartchild, Jr. Distinguished Research Professor and Director of the Program for Lung and Vascular Biology at the Manne Research Institute.

Research at Ann & Robert H. Lurie Children's Hospital of Chicago is conducted through the Stanley Manne Children's Research Institute. The Manne Research Institute is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children's is ranked as one of the nation's top children's hospitals in the U.S.News & World Report. It is the pediatric training ground for Northwestern University Feinberg School of Medicine. Last year, the hospital served more than 208,000 children from 50 states and 58 countries.

Ann & Robert H. Lurie Children's Hospital of Chicago

Related Heart Failure Articles:

New hope for treating heart failure
Heart failure patients who are getting by on existing drug therapies can look forward to a far more effective medicine in the next five years or so, thanks to University of Alberta researchers.
Activated T-cells drive post-heart attack heart failure
Chronic inflammation after a heart attack can promote heart failure and death.
ICU care for COPD, heart failure and heart attack may not be better
Does a stay in the intensive care unit give patients a better chance of surviving a chronic obstructive pulmonary disease (COPD) or heart failure flare-up or even a heart attack, compared with care in another type of hospital unit?
Tissue engineering advance reduces heart failure in model of heart attack
Researchers have grown heart tissue by seeding a mix of human cells onto a 1-micron-resolution scaffold made with a 3-D printer.
Smoking may lead to heart failure by thickening the heart wall
Smokers without obvious signs of heart disease were more likely than nonsmokers and former smokers to have thickened heart walls and reduced heart pumping ability.
After the heart attack: Injectable gels could prevent future heart failure (video)
During a heart attack, clots or narrowed arteries block blood flow, harming or killing cells in the heart.
Heart failure after first heart attack may increase cancer risk
People who develop heart failure after their first heart attack have a greater risk of developing cancer when compared to first-time heart attack survivors without heart failure, according to a study today in the Journal of the American College of Cardiology.
Scientists use 'virtual heart' to model heart failure
A team of researchers have created a detailed computational model of the electrophysiology of congestive heart failure, a leading cause of death.
Increase in biomarker linked with increased risk of heart disease, heart failure, death
In a study published online by JAMA Cardiology, Elizabeth Selvin, Ph.D., M.P.H., of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues examined the association of six-year change in high-sensitivity cardiac troponin T with incident coronary heart disease, heart failure and all-cause mortality.
1 in 4 patients develop heart failure within 4 years of first heart attack
One in four patients develop heart failure within four years of a first heart attack, according to a study in nearly 25,000 patients presented today at Heart Failure 2016 and the 3rd World Congress on Acute Heart Failure by Dr.

Related Heart Failure Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Jumpstarting Creativity
Our greatest breakthroughs and triumphs have one thing in common: creativity. But how do you ignite it? And how do you rekindle it? This hour, TED speakers explore ideas on jumpstarting creativity. Guests include economist Tim Harford, producer Helen Marriage, artificial intelligence researcher Steve Engels, and behavioral scientist Marily Oppezzo.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".