A University of Maryland-led study has identified Angiopoietin-2 (Ang2) as a potential therapeutic target for Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic disorder causing accelerated aging in children. The research, published in Aging Cell, suggests that Ang2 could mitigate cardiovascular complications, a leading cause of mortality in HGPS patients. These findings offer a promising avenue for developing new treatments for this devastating condition, potentially improving the quality of life and extending the lifespan of affected individuals.
The research team, led by Professor Kan Cao, focused on endothelial cells, which line the vascular system and regulate the movement of substances in and out of the bloodstream. Endothelial dysfunction is a known contributor to cardiovascular disease, stroke, blood clots, and atherosclerosis, all of which are prevalent in HGPS. The study revealed that Ang2, a protein involved in blood vessel formation and regulation of blood vessel wall permeability, is significantly impaired in individuals with progeria, affecting endothelial cell function.
Ang2's Impact on Endothelial Cells
The researchers discovered that Ang2 could "rescue" endothelial cells, improving their health despite the dysfunction caused by HGPS. Specifically, Ang2 enhanced blood vessel formation, normalized cell migration, and restored nitric oxide levels, which are crucial for a healthy vascular system. According to lead author Sahar Vakili, "Ang2 treatment also improves endothelial cell signaling to vascular smooth muscle cells, suggesting it could be a potential therapy for vascular dysfunctions in HGPS."
Implications for Progeria Treatment
Currently, treatments for HGPS primarily focus on managing the risk of complications like heart attack and stroke, without addressing the underlying disease mechanism. While Professor Cao acknowledges that this research is unlikely to provide a definitive cure for progeria, she believes it could significantly improve patients' health and extend their lives. "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," Cao stated.
Next Steps
Professor Cao's team plans to conduct a follow-up study in collaboration with the NIH to investigate different methods of administering Ang2 to animal models with progeria. This research aims to optimize the delivery and efficacy of Ang2 as a potential therapeutic intervention. With each study, Cao expresses increasing optimism about finding a cure for progeria, stating, "We are getting really close to a cure for progeria. Research-wise, we are pushing hard, and I can see the light at the end of the tunnel."
