Children with progeria appear normal until they're 6 months to a year old, but then begin developing symptoms normally associated with old age -- wrinkled skin, hair loss, brittle bones and atherosclerosis, which usually causes their deaths by about age 13. There's no known treatment.
But the new Hopkins research, and similar results from other labs, shows that a class of drugs known as farnesyl transferase inhibitors, or FTIs, can reverse an abnormality in laboratory-grown cells engineered to mimic cells from progeria patients. Such cells have nuclei that aren't round like normal nuclei but instead have multiple "lobes" and can even look like a cluster of grapes or bubbles.
In the laboratory, however, treating these engineered cells with an FTI already in clinical trials in cancer patients restored the cells to a normal appearance, the researchers report Sept. 26 in the advance online section of the Proceedings of the National Academy of Sciences. The drug blocks the first step in processing the faulty protein that causes the syndrome.
"We've been hopeful that our two decades of research on how proteins are processed and modified in cells might ultimately help people with certain forms of cancer," says Susan Michaelis, Ph.D., professor of cell biology at Johns Hopkins' Institute for Basic Biomedical Sciences.
"But for progeria, we and others only recently learned that it involves the one of the modified proteins we've been studying, a nuclear protein called lamin A. As a basic scientist, it is really exciting to have leapfrogged from studying a fundamental process to finding evidence that an existing drug might be useful in treating a devastating disease in children," she says.