Tracking the progression of Huntington’s Disease

Huntington’s Disease (HD) is one of those rare diseases for which we know the exact genetic cause. If either of your parents bequeathed to you a huntingtin gene with extra CAG repeats, you will one day succumb to this terrible illness. This means that if you have a family history of HD, you can choose to have yourself tested and thus learn your inevitable fate, at least with regards to HD.

Graphic showing the excessive repetitions of the cytosine-adenine-guanine (CAG) nucleotide sequence in a gene from a Huntington's disease patient (bottom) compared to a gene from a person without the neurodegenerative disorder (top). Credit: National Institute of General Medical Sciences, National Institutes of Health

There is one more implication of being able to test for HD. It means that doctors can now follow the progression of an illness in people who are completely asymptomatic but who will one day have that disease. This kind of certainty is very unusual in medicine. Even with the best family histories, you can’t know for sure if someone will one day succumb to Alzeimer’s or cancer.

Sarah Tabrizi of the University College London and her colleagues, including TRACK-HD (a multinational prospective observational study of HD) investigators, chose to take advantage of this circumstance. They enrolled close to 400 volunteers who had the HD genetic marker but who were asymptomatic. The subjects were followed for thirty-six months. During that time, they were tested for cognitive and motor skills and had periodic brain scans to detect any loss of white or gray matter. Not surprisingly, the subjects showed steady declines in many of these areas. More importantly, the doctors could use the data to construct a sequence of expected failings.

At first glance, this may seem like the world’s most depressing clinical study. Actually, it still seems that way after multiple glances. However, it’s important to keep in mind that the better HD is understood, the more chance there is for a cure. These data could also help doctors learn how to postpone or ameliorate the worst of the symptoms. Barring that, knowing the way the disease progresses could at least give people a more accurate assessment of their futures.

Tabrizi, S., Scahill, R., Owen, G., Durr, A., Leavitt, B., Roos, R., Borowsky, B., Landwehrmeyer, B., Frost, C., Johnson, H., Craufurd, D., Reilmann, R., Stout, J., & Langbehn, D. (2013). Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington's disease in the TRACK-HD study: analysis of 36-month observational data The Lancet Neurology DOI: 10.1016/S1474-4422(13)70088-7.