rare diseases

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Life Of Riley: On Into The Unknown For Rare Girl With Rare Disease

This is the final installment in a special CommonHealth/WBUR series, The Life of Riley: A Rare Girl, A Rare Disease. It’s the story of Riley Cerabona, a remarkable ten-year-old girl born with an incurable, one-in-a-million disease that creates increasingly aggressive “lumps and bumps” on and in her body. So far, the only treatment for her disease, CLOVES syndrome, has been surgery. But this year, at Boston Children’s Hospital, Riley began taking an experimental drug in hopes that it would help her. See the full series here, and the introduction here.

Something was wrong. Riley was limping and her legs felt oddly tired, weakening; they tended to buckle when she took a step.

Could it be the sirolimus, the experimental drug she was taking? Would she have to drop it? Or was it yet another dangerous growth in her spine, caused by her exceedingly rare disease? Would she need one more risky operation?

Late summer was a time of dread for the Cerabona family. But MRIs of Riley’s brain and spine showed no new growths, and blood work suggested that the leg weakness was likely caused by an elevated muscle enzyme. The weakness passed, yet another threat averted — yet another dip and swoop in a roller-coaster year that has, overall, been an unusually fine one.

Riley sums up: “”It was a good year. This year I had fun, did stuff like surfing, drama called River Glee and boogie boarded and skiied, hung out with friends and didn’t have any surgeries. Life to me is like a brownie. Because you eat it slowly and you savor it. And if you savor it there will always be a bite left. (Plus a brownie is one of my favorite foods).”

Indeed, unlike so many past years, Riley underwent no major surgery and needed no extensive rehabilitation. No twisted nest of malformed blood vessels infested her spine and threatened her life; no huge pouch of lymphatic fluid swelled on her torso. And earlier this month, in a small exam room at Boston Children’s Hospital, she happily downed her last dose of the viscous sirolumus (si-ro-LI-mus) that has marred mealtimes for almost a year, and stuck out her tongue one last time at the nastiness.

Riley Cerabona celebrates her last dose of nasty-tasting medicine.  (Jesse Costa/WBUR)

Riley Cerabona celebrates her last dose of nasty-tasting medicine. Behind her: Dr. Cameron Trenor. (Photo: Kristen Davis)

After 48 weeks, her time on the sirolimus trial was over, and that juncture required a decision: Would she remain on the drug, apart from the study?

It might seem like a no-brainer: She had a good year on the drug; stay on it. But it is not so simple.

“The hard thing about this is that you don’t really know,” Marc Cerabona, Riley’s father, said. “And we knew this at the beginning, going into it. We don’t know if she had a good year because of the sirolimus or if she was just going to have a good year this year anyway. But the bottom line for us is, she had a good year and there were no significant side effects. So if there’s a chance that was related to the sirolimus, then why not stay on it? The doctors want to hear a compelling reason to stay on it; we almost want to hear a compelling reason not to be on it.”

Dr. Cameron Trenor, the Children’s specialist overseeing Riley’s trial here: “This is the problem in rare diseases — that everything is an unknown. That’s not talked about a lot. Families live with it every day, so they know it very well, and in pediatrics dealing with rare diseases, I guess we get a little used to it, but everything is new. And the tendency, which is just human nature, is to expect whatever happened to your last patient to represent the whole story, but I can tell you lots of cases where that’s not true. And it’s a real challenge in rare diseases, living day in and day out with the unknown.”

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First Treatment Found For Rapid-Aging Disease In Children

progeria

Researchers have found the first treatment for progeria, a rare “rapid aging” disease in children. (Courtesy of the Progeria Research Foundation)

I first heard of progeria in “When Bad Things Happen To Good People,” by Harold Kushner. The author, a Natick rabbi, lost his 14-year-old son to the disease, a rare genetic defect that causes accelerated aging and effectively turns children into little old people, afflicted by strokes and heart attacks. They die young, of old age.

So my first reaction to today’s big news about the first promising treatment for progeria was: “Now at least the bad things that happen to some good people may not be quite so bad.”

A paper just published in the Proceedings of The National Academy of Sciences reports on a clinical trial for the first known treatment for progeria, and the findings are highly promising. The drug used, Lonafarnib, originally aimed at fighting cancer, appeared to help with weight, bone structure, and most importantly, artery health in 28 children with progeria.

That the drug appeared not only to slow but to reverse some aspects of damage to the children’s blood vessels “is a tremendous breakthrough, because cardiovascular disease is the ultimate cause of death in children with progeria,” said Dr. Leslie Gordon in the press release. She is the lead author of the study, medical director for the Progeria Research Foundation, and the mother of a child with progeria. (She’s also affiliated with Boston Children’s Hospital, Harvard, Brown and Hasbro Children’s Hospital.)

I challenged her on “breakthrough” — I tend to be so cautious with that word that I’m downright allergic to it. Her justification:

“This is a 100% fatal pediatric disease and we had no idea whether it could be influenced in any way by any drug treatment.’

“I do think it can be called a breakthrough, and the reason is that prior to this study finding, we had no idea whether we could offer anything for progeria at all. This is a 100% fatal pediatric disease and we had no idea whether it could be influenced in any way by any drug treatment.

So to me, the breakthrough here is that we have findings that show that progeria can be altered. Not only in the rate of weight gain but that the vasculature can be influenced and the bone can be influenced. That’s a real breakthrough that gives us tremendous hope that by finding more treatments and more ways to get at the disease process in progeria — with the protein called progerin — that we can actually have an impact on the disease.”

The clinical trial was only 2-1/2 years long, she noted, so it is not yet known whether the drug’s benefits will translate into longer lives. But “the breakthrough element is really, ‘Oh my gosh, for the first time, we know the disease can be influenced.’”

I also spoke today with Dr. Mark Kieran, senior author of the progeria study and director of pediatric medical neuro-oncology at Boston Children’s Hospital and Dana Farber Cancer Institute. Our conversation, lightly edited:

So it sounds like this is one of those times when science works just as it’s supposed to: Researchers found the gene, figured out what it did, and then corrected it, at least partially?? Continue reading