The greatest fear of new parents is illness for their baby. Sadly, parents whose children born are with the genetic disease progeria may not know for 18-24 months that there is a problem. But a diagnosis can be devastating. Progeria, although rare, causes a child to age prematurely.

According to the Progeria Research Foundation, the average life span of a patient is just 13.

Patients with progeria suffer from growth failure, loss of body fat and hair, aged-looking skin, stiffness of joints, hip dislocation, generalized atherosclerosis, cardiovascular (heart) disease and stroke. Ultimately atherosclerosis, heart disease, is the cause of early death.

Maybe there’s hope.

Scientists at the National Institutes of Health and the University of North Carolina at Chapel Hill have developed a promising new strategy for treating a form of progeria. A collaboration between the two research facilities are learning that certain anti-cancer drugs known as FTIs can block some of the complex biochemical processes that result in progeria’s symptoms.

“Fortunately, progeria is very rare, and only about one child in four million comes down with it,” Dr. Channing J. Der of the UNC School of Medicine said. “It was first identified in the early 1900s. Since then only 100 or so cases have been found. Still, it is quite devastating for those children who have it and their families.”

Der is working in collaboration with Dr. Francis S. Collins, director of the National Human Genome Research Institute, and Dr. Adrienne D. Cox of the UNC School of Medicine in laboratory. When the NIH began researching the disease, UNC was a natural partner as scientists in Chapel Hill have been working on the drugs for more than a decade.

These potentially lifesaving treatments for progeria of children, also know as as Hutchinson-Gilford syndrome, have had strong, positive effects on the affected cells, but have not yet been used with patients.

FTIs, or farnesyltransferase inhibitors block the action of the enzyme farnsyltransferase. Currently, several chemical variations are undergoing clinical trials with cancer patients.

“There’s a lot of interest in FTIs now because they target an enzyme that’s required for a protein called RAS to cause cancer,” Der said. “The idea that these FTIs also might be useful in treating progeria came up because it turns out that the gene that is mutated in that rare illness also requires this enzyme for generating an active protein known as lamin A.”

The normal maturing process of lamin A doesn’t happen in progeria patients. Instead, a genetic mutation, or damaged form of lamin A is made. Researchers reasoned that the anti-cancer drugs might block the enzyme and hence interfere with the mutated lamin A gene’s haywire actions.

A report on the research has been published in the Sept. 6 issue of the Proceedings of the National Academy of Sciences. Other authors of the report include M.D.-Ph.D. student Brian C. Capell of Collins’ NIH laboratory; NIH staff members Drs. Michael R. Erdos, Renee Varga and Leslie B. Gordon (also medical director of the Progeria Research Foundation); doctoral student James P. Madigan of Cox’s laboratory; Dr. James Fiordalisi, assistant professor of radiation oncology at UNC; and Dr. Karen N. Conneely of the University of Michigan School of Public Health.

“In the paper, we describe experiments showing that the mutant form of lamin A was indeed sensitive to these drugs,” Der said. “The second thing we found was that some of the aberrant biology that this mutant protein causes can be stopped when we treat the cells with the inhibitors.”

Because the drugs already are undergoing clinical trials and much is known about their action and safety, scientists have a significant head start in getting the possible treatment to patients, Cox said. “We are very excited about the possibility that a drug class whose actions we have been working so hard to understand in cancer might soon be useful for this devastating ‘orphan disease,'” she said. “Progeria is clearly an illness that would otherwise get no attention from pharmaceutical companies due to the tiny numbers of children afflicted.”

What’s next in the cause to treat progeria? Cox says enzyme inhibitors testing in mouse models. If experiments succeed, then patient clinical trials may get underway.