Scientists on the trail of treatments for Huntington’s disease may have found a way to track their success. A new study reports that patients with Huntington’s disease have higher levels of expression of a gene called H2AFY in their blood compared with healthy people. What’s more, patients treated with a drug that slows the effects of the disease had reduced levels of H2AFY activity compared with people given a placebo.
The results suggest that H2AFY could serve as a tool for monitoring the progression of the disease and an indicator of whether prospective treatments are working, researchers report online October 3 in the Proceedings of the National Academy of Sciences.
“Biomarker identification for Huntington’s disease is critically important for clinical trials,” says Leslie Thompson, director of the Interdepartmental Neuroscience Program at the University of California, Irvine, who was not involved in the study.
Huntington’s disease is a hereditary movement disorder marked by involuntary bodily twitches and jerks. The damage the disorder does to nerve cells also causes severe depression and impairs a patient’s ability to reason clearly. “It’s a devastating disease,” and one for which there is no cure, says neurologist Clemens Scherzer of Brigham and Women’s Hospital in Boston, who led the new study.
Although some promising treatments are now being tested in clinical trials, one roadblock in their development has been sorting out whether candidate drugs actually halt progression of the disease. To address this problem, Scherzer and colleagues sought a biomarker — a biological indicator they could easily measure — that would provide them with a snapshot of the state of a patient’s disease.
Casting a wide net, the research team analyzed expression data from every gene in the blood cells of more than 100 people. Eight people had Huntington’s disease, and more than 80 had other neurological conditions. Compared with the other participants, the Huntington’s patients had elevated levels of H2AFY expression — levels that were as much as two times higher compared with those of healthy people.
To further study the gene as a candidate biomarker, Scherzer began collaborating with Steven Hersch and colleagues at Massachusetts General Hospital, who were conducting a clinical trial of a compound called sodium phenylbutyrate as a potential therapeutic drug for Huntington’s.
The collaborators measured H2AFY activity in blood cells of trial participants before and after they began taking sodium phenylbutyrate. As patients continued to take the compound, the researchers found decreasing H2AFY activity — a sign that the druglike compound might be slowing the nerve-cell damage inflicted by the disease.
Scherzer says he hopes that H2AFY and other biomarkers like it will help speed the development of new treatments for the disease. “The key is to make clinical trials for Huntington’s disease more efficient,” he says.