Clues found in mysterious childhood aging disease

By Madison Park, CNN
September 10, 2010 8:11 a.m. EDT

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Megan Nighbor, 10, is part of a clinical trial to determine if anti-cancer drugs could treat the accelerated aging disease.

(CNN) -- Megan's hair was the first clue.

Megan Nighbor was born with a full head of thick, dark brown hair. Her mother, Sandy Nighbor, wondered why her youngest child was so well-coiffed compared with her other children, who barely had any hair at birth.

By the time Megan was 18 months old, those brown locks began to thin. Nighbor noticed less hair to grasp when she tied up a ponytail. She noticed other differences, too.

Why was Megan becoming bald? Why did Megan look so much skinnier and different from other children?

Megan was aging at an accelerated rate.

Nighbor learned that her daughter has a rare genetic condition known as progeria. It causes children to wrinkle, show prominent veins and lose their hair as early as their first year of life.

The sight of an aging toddler has baffled and attracted curiosity. It also may have inspired the F. Scott Fitzgerald short story, "The Curious Case of Benjamin Button."

Despite progeria's rarity in the world (about 65 cases), the disease could provide clues about common risks of aging, such as heart attacks and strokes, which account for more than one-third of all U.S. deaths.

"By studying one of the rarest diseases on Earth, we're truly now discovering more about ourselves," said Dr. Leslie Gordon, medical director of The Progeria Research Foundation. "I find that completely mind-blowing."

"Because aging and heart disease are multifactorial, in order to understand each factor, you have to separate it out," she said, about other elements related to heart disease and aging, such as diet, exercise, etc. "These kids are key to that."

Children with progeria die of heart disease, stroke or heart attack, just like millions of adults. Their average life expectancy is 13 years.

A study published in the journal of Arteriosclerosis, Thrombosis, and Vascular Biology this week identified a protein called progerin, which increases in all bodies as we grow older.

Scientists compared the progerin levels of two deceased children with progeria and 29 cadavers without the disease, who were between the ages of 1 month and 97 years.

Progerin was found in much higher quantity in the arteries of children with progeria.

For the specimens without progeria, the amount of progerin appeared to increase in the body by 3.3 percent for every year of age.

"Now we have a solid grasp, this molecule is present and increases in age," said Gordon, lead author of the study. "We need to explore it and what does it have to do with heart disease."

Brian Kennedy, who is the president and CEO of the Buck Institute for Age Research, said looking into diseases such as progeria and Werner syndrome (a premature aging disease that begins in teenage years or early adulthood), provides a unique window into normal aging mechanisms.

"The motivation for this kind of study comes from these progeria kids, because they many not have every phenotype of accelerated aging. They don't look exactly like an old person, but they do have cardiovascular disease, at a very elevated rate," he said. "It's an interesting question -- whether these kids have something that's just a faster version of what's happening in everybody else."

Advancements in progeria have come at a rapid pace in the last 10 years, which is unusual for orphan diseases.

The Progeria Research Foundation was started after a couple, both doctors, learned in 1998 that their son Sam had the disease. Dr. Leslie Gordon is Sam's mother.

"Basically, we found there was nothing out there," she recalled. "This happens especially with very rare diseases. There was no NIH funding for this disease. Physicians didn't know how to treat children with progeria. We started the foundation to find the cause and the cure for progeria."

In 2003, a team of scientists at the National Human Genome Research Institute, led by Dr. Francis Collins, who is now the director of the National Institutes of Health, discovered a gene mutation responsible for progeria.

This gene, LMNA produces a defective form of a protein called Lamin A, which is supposed to provide the structural scaffolding that holds the nucleus of a cell together. Their findings, published in Nature, suggested that this defective form of protein made the structure of the nucleus unstable, leading to premature aging.

Soon after, a diagnostic test for progeria was developed.

Nighbor, of Dalton, Wisconsin, confirmed her daughter's diagnosis with that progeria test in 2003.

Seven years later, Megan is skinnier than her peers and weighs 31 pounds. The syndrome does not affect her learning or mental abilities, as children with progeria are not affected by Alzheimer's disease or dementia.

As children with progeria get older, they suffer stiffness of joints, hip dislocation and hardening of the artery walls. Fortunately, Megan has not experienced such symptoms.

"There's nothing she can't do," Nighbor said. "I can't get her to sit down. She's always running, riding her bike. She's not sick. It's hard for people to fathom that you have this aging disease. You'd think she'd be sick and coughing, it's different."

Standing under 4 feet tall, she has a student helper at school to help her reach items or adjust her desk.

Like many little kids, Megan is a picky eater, preferring pizza, spaghetti and apples. The difference is Megan, at age 10, takes statins and aspirin to stave off heart disease.

"Progeria to her means, 'I have no hair. I'm tinier, just shorter,'" Nighbor said. "That's kind of all that she knows."

Nighbor hopes that a treatment will be developed soon so that Megan will not have to know the fate of children with progeria. Her hopes hinge on an ongoing trial at the Boston Children's Hospital in Massachusetts.

Megan and 27 other children are receiving a daily cancer drug called farnesyltransferase inhibitors -- FTIs -- to determine whether it could help treat progeria. Scientists are still examining the data, so the findings have yet to be published.

Source: CNN