New Hope Against Disease That Prematurely Ages Children
In April 2011, at the age of just 10 months, Ohio native Carly Kudzia was diagnosed with the rare and fatal premature aging disease known as progeria.
"There was an average life span quoted to me that I shall not repeat," said Carly's mom, Heather Unsinger. "No parent should have to hear those words, nor read them."
Affecting just 1 in every 20 million people, progeria is driven by a genetic mutation that results in a vast surplus of a protein known as progerin. This surplus triggers rapidly progressive cellular damage, culminating in irreversible heart disease. There is no known cure or treatment.
Today, "Carly is -- for the most part -- just like any other 7-year-old," Unsinger says. "She's witty, articulate, happy, energetic, fiercely independent and very active. The list of things that she can do is so long that we don't spend much time on the ones we can't."
But the fact is that children like Carly typically won't live to see their 14th birthday. So, "yes, progeria is awful, and we want a cure," Unsinger said.
That sentiment is shared by Dr. Leslie Gordon, co-founder and medical director of the nonprofit Progeria Research Foundation.
Promise for Treating Progeria
And now, Gordon and her colleagues at Harvard and Brown Universities have some good news: They just reported the results of a small study that represents what Gordon calls "a major breakthrough for clinical investigation in progeria."
The investigation, funded by the foundation, centers on an experimental drug known as lonafarnib.
Originally developed to fight cancer, the drug is known to inhibit the activities of an enzyme that is critical to progerin production. Specifically, the drug blocks the enzyme from hooking up with the progerin protein. In so doing, it stops progerin from attaching itself to the patient's cell membranes, where damage takes place.
In the new study, 27 progeria patients were put on a daily two-dose regimen of lonafarnib pills.
On average, treatment continued for a little over two years, during which time just one patient died. In the same time frame, 9 of 27 progeria patients not treated with lonafarnib died.
Side effects typically occurred during the first few months of treatment, and included diarrhea, nausea and appetite loss.
A second group of 36 patients are continuing to take lonafarnib. So far, just four of the total of 63 lonafarnib patients have died, compared with 17 deaths among 63 untreated patients.
"Lonafarnib is a treatment, not a cure," stressed Gordon. But "this is the first support we have for a single medication influencing the life spans of the children with progeria."
Gordon added that the results, published in the April 24 issue of the Journal of the American Medical Association, are "extremely encouraging, because we now know that we can push this disease towards health."
Gordon, a professor of pediatrics at Brown University's Warren Alpert Medical School, in Providence, R.I., noted that since lonafarnib is not yet approved by the U.S. Food and Drug Administration, its cost is not clear.
However, she said the drug's manufacturer, Merck, provided it for free to the study patients, and that her foundation intends to "advocate for a situation where the patient families would receive the drug at no cost to them." According to the foundation, there are currently 144 registered cases of progeria across 45 countries.
Buying Time for Young Patients
Asked what lonafarnib means to her, Unsinger said, "That I will have more time with my daughter, Carly. When a body is aging eight to 10 times faster than average, how important would an [extra] year or two be? How about five or 10?"
The study results, she added, "shifts the composition of my beliefs from pure hope to part hope, part reality. This is a huge shift."
That thought was seconded by Dr. Fuki Marie Hisama, a professor of medical genetics in the department of medicine at the University of Washington in Seattle. She coauthored an editorial that accompanied the study.
"These results," Hisama said, "are the first of their kind for this rare disease, and represent a significant breakthrough. This study gives hope to children with [progeria] and their families for better outcomes in the future."
Dr. Francis Collins, director of the U.S. National Institutes of Health, offered a similarly upbeat reaction to the findings.
"The results of this clinical trial demonstrate for the first time that rational drug therapy can achieve life extension for children with progeria," he said. "That's very encouraging! But research into additional therapeutic interventions, already well underway, may provide even greater hope for the future."
Still, for Carly's mom, the future remains a day-to-day affair.
"It truly is hard to live in the now while planning for the future," Unsinger admitted, "but in Carly's case this is uber-important.
"We may not ultimately know the long-term effect of lonafarnib for many, many years," said Unsinger. "I, for one, am thrilled and thankful for the opportunity to find out. I imagine each dose adding minutes or hours to Carly's life, giving us more time to find a cure."
There's more on progeria at the Progeria Research Foundation.
SOURCES: Leslie Gordon, M.D., Ph.D., medical director, Progeria Research Foundation, and professor, pediatrics, Warren Alpert Medical School, Brown University, and department of pediatrics, Hasbro Children's Hospital, Providence, R.I., and research associate, department of anesthesia, Boston Children's Hospital and Harvard Medical School, Boston; Fuki Marie Hisama, M.D., professor, medical genetics, department of medicine, University of Washington, Seattle; Heather Unsinger, Ohio; Francis Collins, M.D., Ph.D., director, U.S. National Institutes of Health; April 24, 2018, Journal of the American Medical Association