The U.S. Food and Drug Administration has approved a treatment that could give children with a rare genetic illness that causes premature aging more time to live.
Children with the disease, known as Hutchinson-Gilford progeria syndrome, or progeria for short, often die of heart failure, heart attack or stroke as teenagers. Most children with the disorder die before they reach age 15. The newly approved drug, called Zokinvy, is the first and only approved treatment for progeria and certain related syndromes, the FDA announced November 20.
In clinical trials of 62 children receiving the drug, Zokinvy increased life span by about 3 months on average during the first three years of treatment, compared with another 81 kids who did not take the drug from a separate study that collected their health data. Following children who continued to receive Zokinvy for up to 11 years showed that, on average, kids’ life spans were lengthened by about 2.5 years.
“This is not a cure,” cautions Monica Kleinman, a pediatric critical care doctor at Boston Children’s Hospital who was involved with the clinical trials. “We’ve hopefully extended the life span that [the children] have by slowing the pace of the disease,” but, she says, the drug doesn’t give kids a normal length of life.
An estimated 350 to 400 kids across the world have progeria. For these children, a single mutation in their genetic code upends their health (SN: 2/7/13). That mutation interferes with the gene responsible for making the protein lamin A, which helps hold cells’ nuclei together. Children with progeria end up with higher amounts of a defective protein called progerin, which is similar to lamin A but with an extra piece attached. This protein gets stuck in cells’ membranes and can’t be recycled for fresh proteins, causing the cells to prematurely age and making blood vessels and connective tissue stiffer, Kleinman says.
Everyone makes some progerin, and the body makes more as it gets older, Kleinman explains, but “children with progeria make a huge amount.” Children typically appear normal at birth, but start to show signs of the illness in their first two years of life. Over their lives, these kids experience loss of hair and body fat, joint stiffness, cardiovascular disease and other symptoms of accelerated aging.
Zokinvy, made by the company Eiger BioPharmaceuticals of Palo Alto, Calif., blocks some of that progerin production, lowering the amount that accumulates in kids’ cells. But the oral drug, taken as capsules, doesn’t fully block production, she says, and the amount that patients can receive is limited by the drug’s side effects, which include vomiting, diarrhea and fatigue.
The drug is a “testament to the power of basic research,” says Tom Misteli, a cell biologist at the National Cancer Institute in Bethesda, Md, who was not involved with work on the drug. Zokinvy builds on decades of research on many aspects of the lamin A protein, including the “seemingly esoteric chemical modification” that forms progerin, he says.
“Nobody studying this protein or the modification could have expected it to become a drug target,” Misteli adds. But once the disease-causing gene was identified, researchers zeroed in on the class of drugs that includes Zokinvy as potential treatments.
With the new drug approval, the focus is now to test additional drugs or therapeutics in combination with Zokinvy, Misteli says. That could help lengthen the lives of children with progeria even further. Researchers are also investigating gene therapy approaches, with the goal of fixing the mutation that causes the debilitating illness.