Researchers of Huntington’s disease saw a significant breakthrough in June this year when scientists at the University of British Columbia’s Centre for Molecular Medicine and Therapeutics reported a cure for mice with the gene for the disease. The nature and implications of the finding were discussed at a general information session held at U of T on October 26.
Since the exact location of the gene responsible for Huntington’s was discovered in 1993, research on the disease has advanced by leaps and bounds. For those affected by the disease today, the new finding is instrumental in developing a cure.
“This discovery has been ten years in the making,” said Dr. Rona Graham, a post-doctoral fellow at UBC and the lead author of the June 2006 study.
Huntington’s disease is a genetic, degenerative neurological disease passed from parent to child. The gene for it is dominant, which means that an individual has a 50 per cent chance of having the disease even if only one parent is affected. Affected individuals show symptoms around their mid 40s, usually after they’ve passed the gene on to their children. Huntington’s causes significant deterioration of the brain resulting in a slow loss of control in movement, memory, and the ability to make decisions and control emotions.
The gene for Huntington’s encodes a defective protein that is at the root of disease symptoms. In 1996, Graham’s team discovered that there was cleavage of the protein in people with the disease. They hypothesized that this cleavage, and the enzyme that enacts it, called caspase 6, might be the cause of the disease, and pursued this theory for the next ten years.
The team created a mouse model of Huntington’s that expressed symptoms perfectly reflecting those seen in human patients. Using these mice, they altered caspase 6 for one group of diseased mice, and found that they did not show symptoms. Measurements of the striatum, the affected part of brain, also confirmed this fact-the altered HD mice showed normal brain mass.
“We wanted to ensure that the neurons were not only alive but functioning properly,” explained Graham. To test this, behavioural and physical tests were performed on the mice, with successful results.
Currently, researchers are looking for enzymes that can cross the blood-brain barrier and stop the cleaving action of caspase 6. But the development of a treatment for patients is not yet in the foreseeable future, because finding an inhibitor of caspase 6 will be a “tricky” process. If an inhibitor is found, its effects on the human brain and body will have to be tested and researchers will have to determine whether inhibiting caspase 6 will affect the other roles of the enzyme in the brain. However, Graham remains optimistic about the future of research on the disease that afflicts one in every 10,000 Canadians.
“Now that we have identified caspase 6 as a critical player, we have a focus for future research,” Graham said.
Since the progression of Huntington’s is similar to other neurodegenerative diseases, this significant discovery may help in the research of other neurological disorders, said Graham.
“Right now, we have all the tools to further this research,” said Graham. “Our real obstacles are [gaining] financial support.”