Children with progeria age too quickly, developing symptoms common in much older people, such as joint stiffness and heart disease. While most progeria research surrounds the genetic mutation that causes the disease, a team from Houston Methodist is trying to slow aging by targeting telomeres, the caps at the ends of chromosomes.
Progeria is caused by mutations in the LMNA gene, which results in the production of an altered version of the lamin A protein. This abnormal version makes the membrane around a cell’s nucleus unstable, and the cell dies prematurely. Current treatments focus on managing symptoms, but the Houston Methodist team wants to do more.
"These kids are dying of heart attack and stroke at 13, 14, 15 years old," said John Cooke, M.D., department chair of cardiovascular sciences at Houston Methodist Research Institute, in a press release. “Although current therapies are useful, they only add a year or two, on average, to the child's life. We wanted to do something that would improve the children's quality of life and potentially allow them to live longer.”
The team looked at telomeres, found at the tips of chromosomes, which become shorter as cells divide and as we get older. In children with progeria, they shorten at an accelerated rate.
The team used a method called RNA therapeutics to counteract this shortening and rejuvenate the cells. They delivered RNA that codes for telomerase—which can lengthen telomeres—to cells. Then the cells’ machinery took over and began producing telomerase. While the cells only expressed telomerase for a few days, the team saw that they lived longer and worked better.
"We looked at many cellular markers of aging and weren't expecting to see such a dramatic effect on them. Our approach had a much greater effect on all the markers of cellular aging," Cooke said in the statement. "We markedly improved the ability of cells to multiply and reversed the production of inflammatory proteins. Those markers of cell aging we looked at were all reversed with the treatment in our study."
The team plans to advance this treatment toward clinical use, hoping to do so within the next few years, according to the statement. Their goal is to address the unmet need in progeria treatment, but the method could have applications in other aging-related conditions.
“As a physician, many of the diseases I see are due to aging. It's a major risk factor for heart and vascular diseases," Cooke said. "About a third of the people in this country succumb to strokes and heart attacks. If we can fix that, we'll fix a lot of diseases."