Francois Potus

Pulmonary arterial hypertension is a disease in which the blood vessels of the lungs become narrow and stiff. The right side of the heart must then work far harder to push blood through them, and over time it begins to fail. How well that right ventricle holds up is the single strongest predictor of how a patient will do.

Sotatercept is a new drug, recently approved, that has changed what is possible for people living with PAH. It works by rebalancing signals that drive the thickening of lung blood vessels. But something in the clinical trial data does not fit that explanation alone: patients improve within days, far faster than blood vessels can remodel. At the same time, measures of how well the heart pumps did not improve as expected.

Our project asks what else this drug is doing. We will test whether sotatercept relaxes lung blood vessels directly and immediately, which would explain the rapid improvement patients feel, and whether it acts on the heart muscle itself. To do this we use living slices of human lung and human heart tissue that continue to react and beat in the laboratory, alongside a rat model that isolates strain on the heart from disease in the lungs. Our group holds one of the largest collections of PAH lung and heart tissue in Canada.

Understanding the full picture will help doctors know which patients need closer monitoring, and guide the design of safer, more precisely targeted therapies.