Organ Transplant Drug Might Treat Rapid-Aging Disease in Kids

WEDNESDAY June 29, 2011 -- A drug currently used to fight rejection in organ transplant recipients may also reverse DNA cell damage in children with a rare, deadly disorder that leaves them old long before their time, a new study suggests.

Researchers from the U.S. National Institutes of Health and several universities and hospitals used the antibiotic rapamycin on skin cells taken from children with Hutchinson-Gilford progeria syndrome (HGPS), which typically kills sufferers during their teenage years. About 100 cases of progeria have been documented since the disease was discovered at the turn of the 20th century.

Rapamycin appeared to heighten the cells' ability to clear out a toxic protein called progerin, which causes children with progeria to develop skin and joint problems as well as advanced cardiovascular disease that quickly proves fatal. Progerin is present in small amounts in normal human cells and accumulates with age.

"We found it pretty exciting that this drug has such a profoundly positive effect on cell cultures," said NIH Director Dr. Francis Collins, co-author of the study. "The ability to understand the molecular basis [of diseases] and develop targeted therapies makes this a very exciting time to be a physician."

The study is published June 29 in the journal Science Translational Medicine.

In 2005, researchers announced that a class of cancer-fighting drugs called farnesyltransferase inhibitors (FTIs) might prevent the cellular flaw behind progeria. Rapamycin targets a different pathway than FTIs, meaning the combination may someday prove to be a one-two punch to progeria, said Dr. Leslie Gordon, medical director and co-founder of the Progeria Research Foundation and the mother of a teenage son with the disorder.

Because these drugs are already approved by the U.S. Food and Drug Administration for other conditions, their safety is well-established and the approval process to be repurposed for progeria may be streamlined, Gordon said.

"We're incredibly fortunate here... we have a wealth of information to draw from," she said. "We have the potential to attack progeria from different angles. I like that this comes at progerin in a completely different way."

Collins said a drug similar to rapamycin called everolimus, which targets the same molecular pathways, has already been evaluated in clinical trials with children and would likely be the drug used in clinical trials for progeria. While a timeline for such trials is uncertain, Collins said it might be only a few years before researchers know if children with progeria could benefit.

The experiments may also reveal clues about the normal aging process and how to potentially slow it down, Collins said.

"It's clear that this is the same toxic protein also made by you and me, especially as our cells reach the end of their lifespan," he said. "It would be interesting to contemplate if what we learned here can be used to extend our own lifespan."

More information

To learn more about progeria, visit the Progeria Research Foundation.

Posted: June 2011


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