Potential Treatment Method Identified for Huntington's

A team of Harvard researchers have identified a potential method for treating Huntington’s disease that might shed light on treatments for similar neurodegenerative diseases.

The team—led by scientists at the Harvard-affiliated MassGeneral Institute For Neurodegenerative Disease (MGH-MIND)—identified a novel mechanism of clearing disease-causing mutant huntingtin protein from brain cells by modifying the protein structure for autophagic degradation, a natural degradation process in cells.

The introduction of a specific molecular fragment known as an acetyl group into the mutant proteins—a process also known as acetylation—is the key to triggering the destruction of excess huntingtin, according to the findings, which were published in the April 3 issue of Cell.

“The novelty of our research is that it links acetylation to degradation, which hasn’t been shown before,” said Dimitri Krainc, an associate professor of neurology at Harvard Medical School and practitioner at Massachusetts General Hospital, who was involved in the research.

Krainc said acetylation of the Huntingtin protein could be made more efficient through medication, leading to quicker degradation of the mutant protein, and potentially relief from the disease.

Common symptoms of Huntington’s—an inherited disease affecting about 30,000 people in the United States for which there is no known cure—include uncontrolled movements, loss of intellectual faculties, and emotional disturbance.

Current compounds used to increase acetylation lack the specificity that would be necessary to create a safe and efficient medication, Krainc said.

“What we need to do is to find a version of these inhibitors that are more specific for Huntington’s,” he said.

According to Krainc, the study of the accetylation of certain proteins known as histones has been on-going for 40 years, but little is known about the same process in non-histone proteins like huntingtin.

Krainc said that the recent study was taking research on Huntington’s in a new direction—targeting the source of problem.

“There are treatments that are symptomatic, but not targeting the source,” Krainc said. “It’s like when you have a cavity, you take a pain killer, the pain will go away, but the cavity is still there.”

The new study was ground-breaking partly because it has implication for the treatments of other neurodegenerative diseases, Krainc said.

Krainc said that the accumulation of proteins is a “common theme” among all neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases. The hope, he added, is to find more specific drugs that will ablate mutant proteins.

—Staff writer Gordon Y. Liao can be reached at liao@fas.harvard.edu.