Megan Nighbor turned 12 in June, but a rare disease gives her the bones, blood vessels and look of an 80-year-old.
Nighbor has progeria, a disease that speeds up the aging process. It is thought to affect fewer than 250 children worldwide. Nighbor is one year shy of the average life expectancy for progeria patients, most of whom die from strokes or heart attacks at age 13.
But a new drug, originally developed for cancer patients, could help her outlive the odds.
In the first-ever clinical trial for progeria patients, the drug lonafarnib reversed some of the blood vessel changes that cause deadly cardiovascular disease in these pint-size patients. There were also improvements in body weight, bone strength and hearing.
"Does it mean these kids will live longer? We can only know that with time," said trial leader Dr. Mark Kieran, director of pediatric medical neuro-oncology at Boston Children's Hospital and Dana Farber Cancer Institute. "But the fact that we were able to make major changes in the cardiavascular parameters known to be the major cause of death for these kids is pretty exciting."
Twenty-eight progeria patients traveled to Boston from all over the world to participate in the trial.
"At the time, that was about 75 percent of the world's known population," said Kieran, describing the challenge of recruiting enough patients to study such a rare disease. "The ability to bring all the kids here, although expensive and complicated for both us and the families, really allowed us to do this."
The trial results, published Tuesday in the Proceedings of the National Academy of Sciences, come less than a decade after the genetic cause of progeria was discovered.
"It's very gratifying to see evidence of a benefit in this drug trial for kids with this extremely rare disease, and to see it happen so quickly after we found the cause," said Dr. Francis Collins, director for the National Institutes of Health in Bethesda, Md., who in 2003 uncovered the single mutation in human DNA that causes progeria. That's like finding a single spelling error in a book 3 billion letters long.
But the trial might never have happened if it weren't for the Progeria Research Foundation, a non-profit founded in 1999 by Drs. Leslie Gordon and Scott Berns, whose son Sam was diagnosed with the disease.
"Like any parent, we dropped everything," said Gordon, a neuroimmunologist by training who promptly became an expert on progeria. "We quickly discovered there was nothing going on for progeria -- no place for families to go for information, no place for physicians to go to learn how to care for these kids, essentially no hope because no one was taking any action."
The foundation swiftly raised awareness and funds for groundbreaking research, including the 2003 genetic study co-authored by Gordon and Collins.
"Once we found the gene mutation, we didn't have a treatment but we had hope," said Gordon, explaining how the gene defect, which causes a toxic buildup of the abnormal protein progerin, opened the door to treatments. "It didn't seem as unreachable anymore."
Gordon then teamed up with Kieran, who at the time was testing lonafarnib in pediatric cancer patients. The drug helps keep progerin out of the membranous walls of the nucleus -- the cellular control room that guards the body's DNA blueprint.
"Eventually the membrane gets so heavy that it collapses and the cell stops working," said Kieran, explaining how progeria progressively kills the body's cells.
"The ability to repurpose a drug that was actually developed for cancer and turned out to have the right properties for this aging disease was key," said Collins of the quick transition from bench science to bedside treatments. "If you can teach an old drug a new trick, you're a lot closer to the answer than if you're starting from scratch."
It turns out lonafarnib's success in progeria patients also raises hope for healthy adults, whose cells see a slow buildup of progerin over time.
"The kids make a ton of progerin, but it turns out we all make a little bit of it that builds up with age," said Gordon, explaining how blocking progerin might help prevent heart attacks and strokes in the elderly. "By trying to help children with this incredibly rare disease, we've done something to help all of us. We never would have discovered it without them."
All of the trial participants are still taking lonafarnib, only now it's combined with two other drugs that help block progerin buildup even more.
"As a mom, it means that we're moving in the right direction," said Gordon, whose son Sam is now 15 years old. "Not fast enough for me as a parent, of course, but we're moving forward and I'm very grateful for that."
Since starting lonafarnib five years ago, Megan Nighbor has grown a little, her translucent skin has thickened and her bones are stronger, according to her parents.
"We knew we were in good hands from the day we started," said Nighbor's dad, Steve Nighbor. "But to see these changes now and to finally have some hard numbers, you just know that everything Megan's gone through was worth it."
Now in sixth grade, Nighbor is nicknamed "Hollywood" because of her blond wig and big sunglasses.
"She was in a shell when she was younger but she's definitely popped out," said her mom, Sandy Nighbor. "She's not shy anymore."
The Nighbors, who live in the small town of Dalton, Wisc., helped raise $100,000 for the Progeria Research Foundation to fund the $2 million trial.
"Everyone wanted to help," said Sandy Nighbor, recalling a bake sale where her pies sold for $700. "Now we have something we can actually show them and say, 'Look at what you did for us.'"
The Nighbors hope the exciting results fuel even faster progress in progeria research.
"People need to understand we don't have the luxury of time," said Sandy Nighbor. "We need to keep going."