People with Huntington鈥檚 disease show symptoms more than a decade before they are likely to get a clinical diagnosis. These early effects of the disease don鈥檛 affect day-to-day functioning, but they will help drug developers evaluate treatments that target the early stages of the disease.
Huntington鈥檚 is a fatal and incurable brain condition whereby a faulty gene makes brain cells commit suicide en masse. It causes problems in communication, mental processes and movement.
Within the faulty gene, a specific sequence called CAG is repeated too many times. Although 鈥渆nvironmental鈥� factors such as exercise may slow Huntington鈥檚 progression, the number of CAG repeats accurately predicts the age of illness onset. For example, someone with around 40 repetitions is likely to get their first symptoms in late middle age.
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Previous studies have found that several years before the disease manifests itself, the brains of people with the mutation undergo subtle changes, with a thinning of the regions involved in motor function.
To find out whether how these changes affected people with the Huntington鈥檚 gene before clinical symptoms begin, of Monash University in Melbourne, Australia, and colleagues selected 119 people who had the gene but no symptoms. The volunteers were predicted to get clinical symptoms around 10 years later, on average, based on their age and number of CAG repeats.
Circles within rings
Subjects were asked to draw circles within a ring as quickly and accurately as possible for 45 seconds. They then repeated the task, but with their hands obscured and an image of what they were drawing on a screen in front of them, a task which involves more advanced visual-motor coordination.
The team compared this group with 112 people who did not have the gene and 120 people who already had Huntington鈥檚 symptoms.
In the first task, the 鈥減re-manifest鈥� group drew an average of 25 circles in 24 seconds, while those without the Huntington鈥檚 gene drew around 40.
Out of the loop
In the second task the pre-manifest group strayed past the boundaries of the ring more often, says Stout, and took longer to correct errors. 鈥淣ormally, if you see your squiggle is going out of the circle, you correct it,鈥� she says. 鈥淏ut pre-manifest patients were out of the circle for longer.鈥�
On average, for every circle drawn, the pre-manifest group made around three errors, while those without the gene made one.
As expected, those with Huntington鈥檚 were the slowest and least accurate of all the groups in both tests.
, a molecular biologist at the University of Melbourne, says the study is a convincing demonstration that the Huntington鈥檚 mutation begins disrupting normal cellular events 鈥渧ery early in age and long before clinical diagnosis鈥�, he says. 鈥淭he more we understand about the early stages of the disease, the better able we will be to develop new drugs.鈥�
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