Transplant drug rapamycin may help kids with rare premature aging disease progeria

The antirejection drug rapamycin, commonly used in transplants, may be able to benefit children suffering from the premature aging disease progeria, studies in cells suggest. The lab studies indicate that the drug slows aging in the cells and reverses deterioration by getting rid of toxic proteins that build up in the nucleus and damage DNA, researchers reported in the journal Science Translational Medicine. The team is now planning clinical trials in children with the disorder to test their theories.

Progeria is a rare disease because it is caused by spontaneous mutations and is not passed down from parent to child. It is characterized by dramatic premature aging. Young children with the disorder exhibit features and symptoms of advanced age, including hair loss, diminished subcutaneous fat, premature atherosclerosis and skeletal abnormalities. Such children typically die from heart attack or stroke in their teens.

In 2003, government researchers discovered that the disease is caused by a mutation in the gene for a protein called Lamin A, which helps maintain the normal structure of a cell’s nucleus. As a result of the mutation, the cells produce a toxic protein called progerin, which has also been found to accumulate at a much slower rate in normal cells as they age.

In 2009, cell biologist Kan Cao of the University of Maryland in College Park read a paper which showed that rapamycin extends the lifespan of mice and reasoned that it might be preventing some of the damage to cells associated with aging. On a hunch, she treated some cultured progeria cells with the drug and found that, after three weeks, the cells looked healthier.

In the new study, Cao and her colleagues treated cells from three progeria patients and four healthy individuals with rapamycin in culture. They observed that the progeria cells showed a reversal in the structural alterations of the nucleus that are associated with the disease and less DNA damage. The drug also reduced the symptoms of aging in both the progeria and healthy cells. Dr. Dimitri Krainc of the Massachusetts General Hospital Institute for Neurodegenerative Disease, a co-author, demonstrated that the rapamycin activates an intracellular pathway that initiates degradation of proteins not needed by the cells. The level of progerin in the rapamycin-treated cells declined by half, the team found.

The team is now planning a clinical trial of the drug in children with progeria. Because rapamycin is already approved for use in humans, they can skip over safety trials and look directly at efficacy.