A groundbreaking discovery led by the University of Maryland might lead to the creation of innovative and more effective treatments for Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic condition without a known remedy that accelerates the aging process in children.
Published on October 18, 2024, in the journal Aging Cell and in partnership with scientists from the National Institutes of Health (NIH) and Duke University, the study pinpointed a protein associated with the cardiovascular well-being of animal models with progeria, which could inform treatment for humans. Heart failure and strokes are the primary causes of death in individuals with HGPS, who generally have a life span of only 6 to 20 years.
According to Sahar Vakili, a Ph.D. student in biological sciences and lead author of the study, these latest discoveries from the lab of UMD Cell Biology and Molecular Genetics Professor Kan Cao are considered “highly promising.”
“This research could open up avenues for new treatments focusing on cardiovascular issues in HGPS, a significant cause of death among affected children,” Vakili remarked. “Furthermore, the knowledge we gain might also apply to other diseases associated with aging where endothelial dysfunction plays a role.”
Often referred to as “Benjamin Button disease,” HGPS leads to numerous signs typical of aging, such as wrinkled skin, stiff joints, and the loss of hair and body fat. This condition is caused by a mutation in the LMNA (lamin A) gene, which produces a protein essential for maintaining cell health.
To gain a clearer understanding of how progeria leads to cardiovascular issues, the research team focused on endothelial cells, which line the vascular system of the body, including the heart, and regulate the movement of substances into and out of the bloodstream. Dysfunction in these cells can result in various health problems, including cardiovascular diseases, strokes, blood clots, and atherosclerosis (the buildup of plaque in arteries).
The researchers specifically aimed to uncover the signals from endothelial cells that contribute to HGPS-related cardiovascular problems. For the first time, they found that Angiopoietin-2 (Ang2)—a protein that plays a critical role in creating new blood vessels and managing the flow of materials through blood vessel walls—is significantly diminished in people with progeria, detracting from the overall functionality of their endothelial cells.
The team found that Ang2 could be utilized to “rescue” endothelial cells, boosting their health even when affected by HGPS dysfunction. This intervention enhanced blood vessel growth, normalized cell movements, and even restored nitric oxide levels, which are vital for a healthy circulatory system.
“The treatment with Ang2 also enhances the communication between endothelial cells and vascular smooth muscle cells, indicating it might serve as a potential treatment for vascular issues in HGPS,” Vakili noted.
Current HGPS treatments help to mitigate the risks of life-threatening complications like heart attacks and strokes, yet they do not address the underlying disorder itself. Professor Cao pointed out that while their study is unlikely to uncover a definitive cure for progeria, it might extend the lives of patients by enhancing their overall health.
“Since Ang2 only interacts with receptors on endothelial cells, it might positively influence other types of tissues beyond the cardiovascular system, such as bone and fat, as blood vessels are crucial for transporting nutrients, oxygen, and waste in our bodies,” said Cao, who began her research on progeria in 2005, shortly after the cause of the disease was identified.
As a subsequent step, Cao intends to carry out a follow-up study in partnership with a team at the NIH to investigate various methods for administering Ang2 to animal models with progeria.
While the research is ongoing, Cao is optimistic that each new study will bring researchers closer to finding a cure.
“We are nearing a potential cure for progeria,” she expressed. “In terms of research, we are making significant strides, and I can see the light at the end of the tunnel.”
