UC San Diego researchers found an imbalance of opposing cell signals that causes a deadly disease, and they discussed a novel monoclonal antibody therapy.
Participants with “high blood pressure in the lungs, in which blood vessels are narrowed, blocked or destroyed,” can experience cardiac weakness and failure.
The disease is rare, but affects 100,000 people in the US and there are 20,000 deaths each year. There is no cure.
Researchers at the University of California San Diego School of Medicine have published a study that explains the signaling pathway behind PAH, and a novel antibody treatment.
When there is too much JAGGED-1 and NOTCH in the pulmonary small arteries, they cause it to become narrowed. This decreases the flow of oxygen in the body.
The researchers found that overexpression of the NOTCH3 ligand, JAGGED-1, spurs vSMC proliferation but the NOTCH3 ligand DELTA-LIKE 4 inhibits it. They then developed a therapeutic monoclonal antibody that selectively blocks JAGGED-1-induced NOTCH3 signaling, effectively reversing pulmonary hypertension in two rodent models of the disease without toxic side effects.
This study revealed two opposing roles of NOTCH ligands. Importantly, it opens the door to a potentially new safe treatment for PAH using a monoclonal antibody that selectively inhibits activation in the lung vasculature.
