Blocking a microRNA reverses deadly lung disease in preclinical study

Researchers identified microRNA-224 as a promising, first-in-class treatment target for pulmonary arterial hypertension, a rare disease that damages the blood vessels in the lungs.

Researchers blocked a naturally occurring molecule to reverse pulmonary arterial hypertension in preclinical models, a finding that could point to a new treatment approach for people with a rare and often fatal lung disease.

Pulmonary arterial hypertension, or PAH, damages the blood vessels in the lungs and makes it harder for the heart to pump blood.

It affects the heart’s right ventricle that supplies oxygen rich blood to the lungs and, if left untreated, can lead to heart failure and death within two to three years after diagnosis.

In a study published in Science Translational Medicine and led by Yassine Sassi of the Fralin Biomedical Research Institute at VTC, researchers focused on microRNA-224, which was found at elevated levels in the lungs of patients with the disease and in patient-derived cells.

The researchers found that higher levels of the molecule cause cells in the lung’s blood vessels to grow and multiply in ways that worsen the disease.

When the team blocked the molecule using two different approaches — a targeted drug-like therapy and a gene therapy technique — they reversed key signs of the disease in animal models, improving blood vessel function and heart performance and increasing survival in more severe cases.

Unlike more standard gene therapies that replace faulty genes, this approach delivers genetic material into lung cells to block a signal that drives the disease.

“One of the most fascinating findings in this study is that this molecule can regulate several genes within a single pathway — one of the most important in this disease,” said Yassine Sassi, the study’s senior author.

“We’ve been able to show that targeting this molecule can reverse the disease in multiple models, pointing to a new direction for developing treatments that address the underlying cause of the disease.” Current treatments for pulmonary arterial hypertension are primarily palliative, focusing on easing symptoms and improving blood flow but do not cure the disease.

The study found that the molecule disrupts a key balance inside cells that normally controls the thickening of blood vessel walls, and blocking it helps reverse the pathological process by restoring that balance.

The report adds to ongoing university-led research relevant to veterinary medicine, animal health, and clinical decision-making.

university website: Virginia-Maryland College of Veterinary Medicine