UBC research may explain why some people with Huntington’s develop symptoms earlier

Researchers at UBC’s Centre for Molecular Medicine and Therapeutics and BC Children’s Hospital Research Institute say they have identified a clue to why some people with Huntington disease develop symptoms 10 to 12 years earlier than others.

A study published Monday in the scientific journal Neuron found that a particular genetic variant appears to accelerate the disease by driving runaway DNA changes in the brain’s most vulnerable neurons.

Senior study author Dr. Michael Hayden, a professor at UBC’s Centre for Molecular Medicine and Therapeutics and an investigator at BC Children’s Hospital Research Institute, said people with the variant have a dramatically earlier disease onset, though the reason had not been understood. He said the findings show that repeated expansion of the mutation is an important driver of Huntington disease and a potential treatment target.

UBC describes Huntington disease as an inherited, progressive disorder that causes involuntary movements and psychiatric problems. The mutation is present in every cell in the body, but the damage is mainly centred in nerve cells in the brain.

According to UBC, people with the genetic variant had much larger expansions of the Huntington mutation in their neurons. The expansion occurred about five times more often than in patients without the variant.

The results may help explain why Huntington disease primarily affects the brain despite the mutation being present throughout a patient’s body. The authors say the study provides some of the strongest evidence to date that mutation expansion is a key factor in disease progression. Hayden said suppressing that expansion may make it possible to delay progression or the onset of the disease.