The first clinical study of a drug to treat progeria, a fatal disease that causes early-onset aging in children, was published Monday in the Proceedings of the National Academy of Sciences. The study was led by Leslie Gordon MA'91 MD/PhD'98, associate professor of pediatrics at Alpert Medical School.
Though the drug does not cure progeria, the study is an "incredible first start," said Scott Berns, Gordon's husband, clinical professor of pediatrics at Alpert Medical School and chair of the board of directors of the Progeria Research Foundation, which he and Gordon founded in 1999, after learning that their son had progeria.
Progeria is a rare disease that affects around one in every four to eight million children. When children are around one and a half to two years old, they start to experience symptoms associated with aging such as an inability to gain weight, joint stiffness and heart disease, among others. The disease has a 100 percent fatality rate, with children usually dying of heart disease around age 13.
The disease is caused by a genetic mutation, which researchers discovered in 2003. This mutation causes production of the abnormal protein progerin.
Researchers realized that a class of drugs developed to treat cancer could potentially block the attachment of one of progerin's subunits, reducing the negative effects of the disease, Gordon said.
In the clinical trial, researchers tested an adapted version of the cancer drug, lonafarnib, on 26 children with progeria over the course of two years. One patient died of a stroke midway through the study, but of the 25 children who took the drug for two years, all but one showed some form of improvement, including weight gain, less skeletal rigidity and less stiffness in their arteries.
Children in the study experienced some negative side effects including diarrhea and loss of appetite, but none of these effects caused any participants to drop out of the study, Gordon said.
Gordon said their results far exceeded her expectations. Before the trial, researchers did not even have baseline data on the abnormalities in bone density and the cardiovascular system that progeria causes, she said.
"The ability to affect those systems is not something we knew we could do. I'm very excited that we made this step forward," she said.
The University and Rhode Island Hospital jointly run the cell and tissue bank that supports the basic science research needed to understand more about the disease, Gordon said. The University's Center for Gerontology and Healthcare Research also contains a medical database with the health information of children with progeria from all over the world. The existence of this database has proven essential, Gordon said.
"The benefits appear modest, so the overall impact of the study needs to be kept in proper perspective," wrote Robert Hegele, a professor of medicine and biochemistry at the University of Western Ontario, in an email to The Herald. Hegele was not involved in this study, but has researched the disease in other contexts. He wrote that the study "provides a great foundation upon which to develop newer forms of treatment that might be even more effective in the future."
Berns said the rate at which progeria research has progressed is "incredible." When their son Sam was diagnosed with progeria, "There was nothing going on. There were certainly no answers," he said. "Look how far we've come."
Though Berns called the study "a dream realized," he said there is a lot more work to do. One key next step is to get approval for the drug from the Food and Drug Administration, he said.
Gordon said they are already in the midst of a second clinical trial in which two more drugs are being tested.
"We need to get more drugs, we need to have more medication, different strategies for attacking progerin ... until we arrive at a cure," Gordon said.