Scientists make surprise finding on what causes Huntington’s disease

globalnews.ca:

Scientists are unravelling the mystery of what triggers Huntington’s disease, a devastating and fatal hereditary disorder that strikes in the prime of life, causing nerve cells in parts of the brain to break down and die.

The genetic mutation linked to Huntington’s has long been known, but scientists haven’t understood how people could have the mutation from birth, but not develop any problems until later in life.

New research shows that the mutation is, surprisingly, harmless for decades. But it quietly grows into a larger mutation — until it eventually crosses a threshold, generates toxic proteins, and kills the cells it has expanded in.

“The conundrum in our field has been: Why do you have a genetic disorder that manifests later in life if the gene is present at conception?” said Dr. Mark Mehler, who directs the Institute for Brain Disorders and Neural Regeneration at the Albert Einstein College of Medicine and was not involved in the research. He called the research a “landmark” study and said “it addresses a lot of the issues that have plagued the field for a long time.”

The brain cell death eventually leads to problems with movement, thinking and behavior. Huntington’s symptoms – which include involuntary movement, unsteady gait, personality changes and impaired judgment – typically begin between the ages of 30 and 50, gradually worsening over 10 to 25 years.

Scientists at the Broad Institute of MIT and Harvard, McLean Hospital in Massachusetts and Harvard Medical School studied brain tissue donated by 53 people with Huntington’s and 50 without it, analyzing half a million cells.

They focused on the Huntington’s mutation, which involves a stretch of DNA in a particular gene where a three-letter sequence – CAG – is