A new study could spur the development of new and improved treatments for Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic disorder with no known cure that causes accelerated ageing in children.
The study identified a protein linked to the cardiovascular health of animal models with progeria that could translate to human treatments. Heart failure and stroke are the most common causes of death for people with HGPS, who typically have a life expectancy between six and 20 years old.
Sometimes called the ‘Benjamin Button disease,’ HGPS causes a variety of symptoms associated with ageing, including skin wrinkling, joint stiffness, and the loss of hair and body fat. The disease stems from a mutation in the LMNA (lamin A) gene, which produces a protein that helps to keep cells healthy.
To better understand how progeria causes cardiovascular complications, the research team looked at endothelial cells.
These cells line the body’s vascular system—including the heart—and control substances moving in and out of the bloodstream. When endothelial cells malfunction, it can lead to an array of conditions, including cardiovascular disease, stroke, blood clots and atherosclerosis (buildup of plaque inside the arteries).
More specifically, the researchers wanted to understand the signals sent by endothelial cells that ultimately lead to HGPS-related cardiovascular disease. For the first time, the team discovered that Angiopoietin-2 (Ang2)—a protein that regulates the formation of new blood vessels and the flow of substances through blood vessel walls—is significantly impaired in individuals with progeria, affecting the overall function of their endothelial cells.
The researchers discovered they could use Ang2 to “rescue” endothelial cells, improving their health despite dysfunction stemming from HGPS. It enhanced the formation of blood vessels, normalised cell migration and even restored nitric oxide levels, which are crucial for a healthy vascular system.
Current treatments for HGPS can help reduce the risk of fatal complications like heart attack and stroke, but they do not target the underlying disease.
“While Ang2 only has receptors on the endothelial cells, it may have a broader beneficial impact on additional tissue types beyond cardiovascular systems, such as bone and fat tissues, since blood vessels are essential for our body to transport nutrients, oxygen and waste,” the researchers said.
The study was led by the University of Maryland.
Lead author Sahar Vakili said: “This could pave the way for new treatments targeting cardiovascular complications in HGPS, which are currently a major cause of mortality in the affected children.
“Beyond progeria, insights gained from this research might also be applicable to other age-related diseases where endothelial dysfunction plays a role.”
