In the spring of 2005, families affected by progeria welcomed the news from two studies that uncovered new information about this rare, devastating condition that causes premature aging in children. Now both parents and pediatricians are hopeful that researchers may be on the brink of improving the odds for these children.
According to the National Institutes of Health, progeria—formally known as Hutchinson-Gilford progeria syndrome—affects about 1 in every 8 million children. Although these children look healthy when they are born, they begin to show symptoms of premature aging between 18 and 24 months. They experience slow growth, lose weight and hair, and have narrow, often wrinkled faces. In addition, their skin becomes tough, their range of motion becomes limited and they develop diabetes that does not respond to insulin treatment. Over time, the children develop a hardening of their arteries, and they usually die of heart disease or a stroke in their early teens. In other words, they experience the aging process at a much faster rate.
But there is hope. It was recently discovered that progeria develops from a mutated gene that contains the information for creating a protein called lamin A. The resulting abnormal protein affects the structure of a cell's nucleus, so in children with progeria, the nucleus becomes unstable, which leads to premature aging.
In one of the recent studies, published in Nature Medicine, researchers at the National Cancer Institute (NCI) found that cells affected by this condition could be made healthy again by correcting defects in the lamin A protein. The second study, published in the Journal of Pediatrics, found that low levels of HDL, or "good" cholesterol, play a role in the development of heart disease in children with progeria. However, other traditional heart disease risk factors, such as high LDL ("bad" cholesterol), total cholesterol and C-reactive protein, did not influence heart disease development in these children.
Despite the role of this gene mutation, progeria does not run in families. Instead, the mutation is believed to stem from a chance anomaly in the sperm or egg prior to conception.
The disease has traditionally been diagnosed only through physical exam and X-rays. Misdiagnosis has been common, but a genetic blood test that provides a more definitive diagnosis has recently become available.
Treatments for Today and Tomorrow
While there is no treatment for progeria, according to the Progeria Research Foundation, there are steps parents and doctors can take to improve a child's quality of life. For example, children with progeria often have poor appetites, and certain nutritional supplements, such as Pediasure and Boost, can help them get the nutrition and calories they need. This, in turn, can improve their mood, energy levels and skin and hair health.
Likewise, physical or occupational therapy two to three times a week can help children stay active. Additionally, daily low-dose aspirin therapy may be recommended to prevent heart disease, as it is in at-risk adults.
Parents and children with progeria are hopeful that the future will bring therapies that treat the underlying genetic abnormalities. The recent NCI study is a step in that direction.
"There's a lot of work going into these gene therapies, where you get the body to either not read or process a bad message from a gene, or not to express the bad message and cause mischief," says Dr. Leslie Smoot, a pediatric cardiologist and the director of the congenital cardiovascular genetics program at Children's Hospital in Boston.
However, Smoot is quick to point out that it's a long road from accomplishing this in a lab to successfully treating a child.
But the fact that researchers now know it's possible to reverse the cellular defects associated with progeria is "hugely helpful," she says.
As for the prevention of heart disease in children with progeria, Smoot says that the next step in research will be to understand the relationship between the lamin A protein and HDL cholesterol levels. Such research, she believes, could have "huge implications for everybody."
"Aging and heart disease are the two most significant issues for most people in Western society," Smoot points out, "so anything we learn along about progeria might provide clues for the general population."