Anticancer drug may slow aging process

Robin Wulffson MD's picture
aging, progeria, lonafarnib, cardiovascular disease, premature death
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Aging is investable. Many of us invest significant effort in activities focused on slowing the process. We exercise, make dietary choices, pop pills, and invest in cosmetic treatments. A new study focused on a rare childhood disorder may serve to gain insight into how to slow the aging process. Researchers affiliated with Harvard Medical School published their findings on September 24 in the Proceedings of the National Academy of Sciences.

A drug that was developed for cancer has shown promise as a treatment for children who suffer from premature aging. In addition, the drug may have benefits for treating cardiovascular problems associated with normal aging. Progeria, also known as Hutchinson–Gilford progeria syndrome (HGPS), is an extremely rare disease that causes premature aging and early death. Researchers have theorized whether progeria might offer clues into the normal aging process. Over the past few years, papers have been published demonstrating that progerin, a mutant form of the Lamin A protein, which is critical in organizing the genome inside the body's cells, accumulates in all humans as they age. The concept is that a drug that mitigates cardiovascular problems in children with progeria might also decrease the development of cardiovascular disease in the general population.

Children with this multisystem disorder exhibit failure to thrive and accelerated atherosclerosis leading to early death. The children die of heart attacks or strokes at an average age of 13 because of the accumulation of progerin. The researchers note that farnesyltransferase inhibitors have slowed the disease in preclinical studies.

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They note that 25 patients with progeria received the farnesyltransferase inhibitor lonafarnib for a minimum of two years. Primary outcome success was predefined as a 50% increase over pretherapy in estimated annual rate of weight gain, or change from pretherapy weight loss to statistically significant on-study weight gain. Of the 25 patients, 9 experienced a 50% or more increase, six experienced a 50% or less decrease, and 10 remained stable with respect to rate of weight gain. Secondary outcome measures included decreases in arterial pulse wave velocity and carotid artery echodensity and increases in skeletal rigidity and sensorineural hearing. All patients improved in one or more of these outcomes.

The investigators concluded that the results from this clinical treatment trial for children with HGPS provide preliminary evidence that lonafarnib may improve vascular stiffness, bone structure, and audiological (hearing) status. The researchers have another study underway at Boston Children’s Hospital; it involves a cocktail of lonafarnib and two additional drugs. The aim is to determine whether the combination of drugs will be more effective. In addition, a fourth drug is being tested in mice and may be tried in the children in another trial.

Progeria affects about one in four million to one in eight million newborns. Worldwide, an estimated 200 to 250 children live with the disease. Children with progeria die at an average age of 13 of heart attack or stroke. Children with progeria appear healthy when they are born; however, they usually start to show signs of the disease at 18 to 24 months, including failure to thrive, loss of hair, and loss of body fat.

Reference: Proceedings of the National Academy of Sciences.

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