Results of the first clinical drug trial for children with a rare rapid-aging disease, known as Progeria, has shown successfulness with a farnesyltransferase inhibitor (FTI), a drug first used to treat cancer.

The clinical trial results showed significant improvements in bone structure, weight gain, and most importantly, the cardiovascular system, according to new research published in Proceedings of the Natural Academy of Sciences.

Also known as Hutchinson-Gilford Progeria Syndrome (HGPS), Progeria is a rare and fatal genetic disease displaying an appearance of rapid aging in children. The disease becomes fatal when those affected develop the same heart disease (atherosclerosis), as millions of normal aging adults. Instead of this occurring at 60 or 70 years of age, children with Progeria can suffer heart attacks or strokes starting at the age of 5, with the average age of death being 13.

Leslie Gordon, MD, PhD, lead author of the study, medical director for PRF, and mother of a child with Progeria, says:

The two and a half year drug study consisted of 28 children from 16 different countries, accounting for 75 percent of Progeria cases worldwide. Twenty-six of the 28 children had the classic form of the disease. All 28 children traveled to Boston every four months to receive extensive medical testing through Children’s Hospital’s Clinical and Translational Study Unit.

The oral medication, the FTI lonafarnib, was given twice daily over the course of the study. The research team assessed the children’s rate of weight gain, compared to their pre-study rate. They viewed this as the primary outcome because these kids suffer from critical failure to thrive, characterized by extremely slow weight gain over time. Researchers also inspected stiffness of the arteries (a predictor of heart attack and stroke), as well as bone rigidity and density (a predictor of osteoporosis). Every child participating in the study showed significant improvement in weight gain ability, bone structure, or flexibility of blood vessels.

Noteworthy Improvements

A Blueprint For Progeria Treatment
After the discovery of the gene that causes Progeria, FTIs were suggested as a potential drug treatment. These kids have a genetic mutation that produces the protein progerin, which is responsible for the disease. Progerin blocks normal cell function and causes harm to the body via a farnesyl group, a molecule that attaches itself to the protein. FTIs prevent this attachment from happening.

Mark Kieran, MD, PhD, the study’s senior author and associate professor of Pediatrics at Harvard Medical School explains:

The results of this study are extremely encouraging. A second clinical trial funded by the Progeria Research Foundation and the National Institutes of Health is under way, while more are expected to follow.

Previous research has shown that progerin is produced in all humans and increases in the body with age. Several earlier studies have seen associations with normal aging and progerin, including a link between progerin and genetic instability. Investigators plan to continue researching FTIs and their effects, which may help lead to more information about cardiovascular disease as well as the normal aging process that affects every population.

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Written by Kelly Fitzgerald