Dagmar Ehrnhoefer,
New research by the Faculty of Medicine suggests that a strict eating schedule can help clear away the protein responsible for Huntington disease in mice.
Huntington disease (HD) is an inherited, progressive disorder that causes involuntary movements and psychiatric problems. Symptoms appear in adulthood and worsen over time. Children born to a parent with HD have a one in two chance of inheriting the disease, which is caused by a buildup of mutant huntingtin protein (mHTT).
Faculty of Medicine scientists stimulated autophagy—a process in which the cell cleans out debris and recycles cellular material such as proteins—by restricting access to food in mice with HD to a six-hour window each day. This led to significantly lower levels of mHTT in the brain.
“We know that specific aspects of autophagy don’t work properly in patients with Huntington disease,” said lead author Dagmar Ehrnhoefer, who conducted the study while she was a researcher in the laboratory of Professor Michael Hayden, in UBC Centre for Molecular Medicine and Therapeutics. “Our findings suggest that, at least in mice, when you fast, or eat at certain very regulated times without snacking in between meals, your body starts to increase an alternative, still functional, autophagy mechanism, which could help lower levels of the mutant huntingtin protein in the brain.”
Dale Martin
The researchers also uncovered a clue in the mystery of why mice expressing a modified form of the HD gene show no HD symptoms. The genetic modification prevents the mHTT protein from being cut, or cleaved, at a specific site. These mice had higher rates of autophagy than mice with regular, cleavable mHTT, indicating that the cleavage site is important for regulating autophagy.
While current therapeutic strategies to lower mHTT are targeted at the Huntington disease gene, this new research suggests that another potential treatment approach is to stimulate autophagy, either through diet or the development of therapies that target the cleavage site.
Dale Martin, a co-author who conducted the research as a UBC postdoctoral fellow, said the findings, published in Acta Neuropathologica Communications, demonstrate that seemingly small lifestyle changes could have an impact on HD.
“HD is a devastating disease with no cure available at this time,” Martin said. “More studies are needed, but perhaps something as simple as a modified dietary schedule could provide some benefit for patients and could be complementary to some treatments currently in clinical trials.”