Results from a recent study
published in the September issue of The Lancet Neurology by researchers in England and Wales identifies a gene linked to Huntington’s disease (HD) progression.
While the outcomes of the genome-wide association study, led by researchers at Cardiff University and University College London (UCL), hold no immediate prospect or potential for a treatment, the discovery could eventually lead to a means to delay the progression of HD and find better targeting therapies in the future.
HD is a genetic and neurodegenerative condition in which physical, psychological and cognitive overwhelm its patients. Chorea, an abnormal involuntary movement disorder, is the principal physical symptom. Patients typically develop HD around the age of 30, and symptoms will progressively worsen over time. Most people with HD die within 10-15 years of diagnosis, but some progress faster than others, which could be the result of new genes linked to progression.
By using high quality phenotypic data on people with the HD gene mutation, the researchers recognized that varying symptoms of disease progress in parallel, meaning that data from cognitive, motor and MRI brain imaging variables could be combined and compared to produce a progression score for genetic analysis.
The data was obtained from 216 HD patients in the TRACK-HD study, along with 1773 HD patients in the European Huntington’s Disease Network REGISTRY study.
The outcomes showed that several genes link to disease progression, however, the finding with the strongest association was a single point mutation in a gene called MSH3.
“The strength of our finding implies that the variant we identified has a very large effect on HD, or that the new progression measure we developed is a much better measure of the relevant aspects of the disease, or most likely, both,” said Lesley Jones, a professor at Cardiff University in Wales and a co-senior study author in a press release
MHS3 is a DNA repair gene that has been linked to size changes in the HD mutation.
“Now we know that MSH3 is critical in the progression of HD in patients, we can focus our attention on it and how this finding may be harnessed to develop new therapies that slow disease progression,” said Sarah Tabrizi, professor at UCL Huntington’s Disease Centre and second co-senior author of the study.
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