Researchers may have discovered a new way to monitor mitochondrial diseases, a spectrum of disorders caused by genetic errors in mitochondria, the fuel-burning factories within cells that produce energy necessary for life. A new study reveals that people with these diseases may be deficient in glutathione, a toxin-fighting molecule made by the body that helps repair damage wrought by wayward mitochondria.
"We found very clearly that the glutathione levels were low in our mitochondrial disease patients," says Gregory Enns, a pediatrician and geneticist at Stanford University in Palo Alto, Calif. and coauthor of the study published this week in the online edition of the Proceedings of the National Academy of Sciences. By measuring blood levels of glutathione, researchers may be able to assess the severity of a patient's disease and gauge how well therapies are working, Enns notes.
Mitochondrial diseases stem from gene defects in the cells' mitochondria, which convert energy from food into energy the body can use. These genetic errors lead to the production of dysfunctional proteins that spew toxins into the cells. "It's a little bit like a car engine; if it doesn't work well, it produces smoke," Enns says. In mitochondrial diseases, that "smoke" consists of free radicals—unstable molecules such as hydrogen peroxide that damage the cell's DNA, proteins, and lipids (fats), preventing them from functioning properly and causing them to die prematurely.
Scientists have identified over three dozen types of mitochondrial diseases, and the symptoms vary widely depending on which organ or organs, such as the heart, brain and liver, are affected. Newborns with the diseases can suffer seizures and lethal organ failure in the first few days of life, while other patients manage to make it into their 40s and even 50s before experiencing more benign symptoms such as weakness and inability to do physical activity. The severity of these disorders vary immensely, making it difficult to generalize how many years are knocked off the average patient's lifespan, Enns notes. Among the most famous cases of mitochondrial disease: nine-year-old Hannah Poling, whose mitochondrial disorder caused autism-like symptoms that were exacerbated by routine childhood vaccinations.
Mitochondrial diseases affect about one in every 8,500 adults in the U.S. (0.1 percent of the population), and doctors often treat them with cocktails of antioxidants including vitamin C and vitamin E that are believed to combat free radical damage caused by the disease, according to Enns. One key problem, he notes, is that doctors don't really understand how these antioxidants work -- or how effective they are in staving off symptoms in the long run.
In their study, Enns and his colleagues compared blood samples taken from 20 patients with mitochondrial disease ages two to 36 with those of 20 healthy patients ages 25 to 47. Levels of glutathione, a molecule the body makes to combat free radical damage, in the white blood cells of the diseased patients were 20 to 25 percent lower than those in the healthy crew, indicating that the body's ability to fight free radical damage was compromised, according to first author Kondala Atkuri, a biochemist at Stanford.
This study suggests that glutathione blood levels might serve as a good indicator of how large a toll these diseases are taking on the body, which could come in handy in drug trials, Enns says. "Before we can give drugs to patients in a clinical trial," he says, "we need to establish the biomarkers [such as glutathione] to see if treatments are working."
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