MONDAY, July 25, 2005 (HealthDay News) -- Five years ago, Dr. Leslie Gordon was a resident doctor specializing in pediatric ophthalmology. That's when her son Sam, now 8 years old, was first diagnosed with an extremely rare genetic condition called progeria, characterized by accelerated aging.
Besides experiencing joint, skin and other problems, children with progeria develop an accelerated form of cardiovascular disease, with most dying from heart-related complications before the age of 20.
Gordon said she and her husband, Scott Berns, also a doctor, "quickly discovered that there wasn't anything out there" on the disease -- no information on its cause, no reliable diagnostic test, and almost no research into a condition that affects just one in every 4 million people.
Fast-forward to 2005: Thanks largely to the efforts of the Progeria Research Foundation (PRF) -- a group Gordon helped found -- scientists have already identified the cause of progeria (mutations in a single gene), set up a tissue bank necessary for ongoing research, and organized regular scientific meetings to exchange ideas. PRF is also working with the National Institutes of Health to collect data on children with progeria worldwide, as a baseline dataset for their ultimate goal: clinical trials aimed at a cure.
But the implications of progeria research may go far beyond helping children like Sam Berns.
"Studying progeria results in a 'double whammy' for researchers," his mother said. "First, of course, you get to try and save the lives of children who are all going to die from this disorder. But you also get to learn something very important about key elements behind heart disease and aging."
Dr. Samer Najjar is head of the Human Cardiovascular Studies Unit at the National Institute on Aging. He agreed with Gordon that progeria kids can teach researchers a lot about the nation's number one killer.
"These children get heart disease at an incredibly accelerated pace, usually by the time they are 12, 13 or 14," he pointed out. "In the general community, the prevalence of cardiovascular disease starts appearing in the 60s and 70s. Obviously, there's some process that's accelerated."
In the case of progeria, that acceleration starts with a mutation in a gene producing a cellular protein called lamin-A.
"In kids with progeria, that protein goes awry and you create an abnormal protein that we call 'progerin,' " Gordon said. Unlike lamin-A, progerin fails to degrade properly and instead attaches itself to healthy lamin-A and structures in the cell's nucleus. This "spider-like" effect also affects the "downstream expression" of many other genes, Gordon said.
The result is accelerated aging at both the cellular and physiologic level, including the early onset of cardiovascular disease.
In a recent paper published in the Journal of Pediatrics, Gordon lead a team of researchers that discovered key differences between the atherosclerosis ("hardening of the arteries") seen in progeria children and that displayed by aging adults.
"In these kids," Gordon said, "heart disease isn't caused by high cholesterol, at least not high levels of LDL ['bad'] cholesterol." Instead, progeria seems to weaken cellular resistance to daily damage brought about by cell division and blood flow. That added vulnerability to metabolic stress makes children "more susceptible to damage-formed plaques along artery walls," she explained.
But doctors have long known that some adults are more susceptible to atherosclerosis than others, Gordon pointed out.
"Heart disease depends, in large part, on your genetic disposition -- it's not all about cholesterol," she said. "In the last couple of years, progeria research has been teaching us that damage-driven plaque formation is something that we all need to pay attention to in the general population."
Then there's the question of aging itself.
"It's amazing how much progeria resembles the normal aging process," said Dr. Vilhelm Bohr, chairman of molecular gerontology at the National Institute on Aging. "I think these proteins linked to progeria play a very profound role in the aging process, and I think we've already seen some pretty big findings in terms of what these proteins do. Lamin-A, for example, appears to have many roles."
Gordon stressed that progeria doesn't exactly mimic the human aging process -- progeria children aren't especially susceptible to cataracts or cancer, for example. But the disorder "is providing insight into mechanisms that we can study," Bohr said.
In the meantime, the group Gordon founded is busy helping parents of children with progeria better understand the challenges facing their child.
"The first question I get from brand-new parents isn't, 'Are we going to have a cure?' " she said. "It's, 'What is my child going to go through? How can I help their joints, their skin?' It's about the happiness of the child today."
To help parents -- many of whom contact the Progeria Research Foundation from developing countries -- the organization facilitates free Internet and phone hook-ups between families in the same country or region. "We put families together. That's crucial, because they are so lost -- this disease is so rare," Gordon said.
Collaborating with the National Institutes of Health, the foundation is also flying children and their parents from sites around the world to NIH facilities in Bethesda, Md., so that kids can receive a full clinical assessment.
"That's to get a baseline dataset -- you need that data to understand if any drug is working or not," Gordon explained. "That's a great leap of faith, of course -- we don't know for sure that we'll find a cure, but we do know we won't be able to find a cure without doing this study."
Still, the speed of discovery occurring since Gordon started PRF five years is encouraging.
"I'm told all the time, 'Wow, you're moving so fast,' and I do feel that speed," she said. "But I also know that we always need to feel like we can do better. Even if I wasn't the mother of a child with progeria, I still see the faces of other children with progeria every day. So nothing can go fast enough for me."
For more on progeria, head to the Progeria Research Foundation.