The drug rapamycin has been found to reverse the effects of Hutchinson-Gilford progeria syndrome, a fatal genetic disease that resembles rapid aging, in cells taken from patients with the disease. Rapamycin, an immunosuppressant drug used to prevent rejection of transplanted organs, has already been shown to extend life span in healthy mice. Researchers hope the findings will provide new insight into treating progeria as well as other age-related diseases.
Skin cells from patients with progeria show a slew of defects: deformities in their membranes, decreased growth, and early death. Kan Cao, an associate professor of cell biology and molecular genetics at the University of Maryland, and her colleagues found that rapamycin could reverse these defects by enhancing the cells’ ability to degrade the protein progerin, which accumulates in abnormal amounts in progeria patients. The study was published today in the journal Science Translational Medicine.
It’s not yet clear whether the drug will have similar effects on animals or patients. But progeria researchers are planning a clinical trial of rapamycin. No treatments currently exist for the disease, which is typically fatal by age 12. Children with progeria have health issues typically associated with old age, including balding, hardened skin, pain in joints, hip dislocations, and heart disease.
Researchers say the findings could be relevant beyond this rare genetic disease. Although accumulation of progerin is associated with progeria, the protein also accumulates in small amounts in normal cells, and may be partially responsible for the aging process.
Some age-related diseases, such as Parkinson’s and Alzheimer’s, also result in defects in the cells’ “trash-removal” system, says Dimitri Krainc, associate professor of neurology at Harvard Medical School and one of the authors of the paper. In fact, previous research has shown that the failure of cellular maintenance is a key component of aging. “With normal aging … you start accumulating by-products of normal cell functions,” explains Krainc. Rapamycin may be able to help clean up other toxic proteins as well, though this study only looked at its effects on progerin.
“I would hope that the study increases the search for molecules to replace rapamycin,” which don’t have the immunosuppressant side effects, says David Sinclair, director of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging at Harvard Medical School. Such alternatives could be a major step forward in the fight against aging, says Sinclair, who was not involved in the current study.