Rare Disease Report

Study Discovers New Gene Responsible for Huntington's Disease Progression

JULY 06, 2017
Mathew Shanley
Per a British study published in Lancet Neurology, mutations of the MSH3 gene may be associated with Huntington’s disease (HD) progression.
Conducted by researchers from University of College London (UCL) and Cardiff University in Wales, the study, “Identification of genetic variants associated with Huntington’s disease progression: a genome-wide association study” found that the gene could become a biomarker for HD and its identity could lead to future treatment options for this fatal, neurological disease.
HD is due to a mutation on the Huntingin gene and almost always results in the progressive loss of both mental and motor control. Symptoms most frequently show when the patient is between the ages of 30 and 50 years, and progress over a 10 - 25 year period until death.
The new study indicates that the Huntingtin gene is not the only gene involved in disease progression.
"We've identified a gene that could be a target for treating Huntington's disease. While there's currently no cure for the disease, we're hopeful that our finding could be a step towards life-extending treatments," said lead author Dr Davina Hensman Moss of the UCL Huntington's Disease Centre and UCL Institute of Neurology.
"The gene variant we pinpointed is a common variant that doesn't cause problems in people without HD, so hopefully it could be targeted for HD treatments without causing other problems,” Moss continued.
Information captured in both the TRACK-HD study (n=216) and the much larger European Huntington’s Disease Network REGISTRY study (n=1773) were compared, as researchers evaluated the cognitive and movement symptoms in both. Symptoms and the disease’s progression with the genetic mutations in the combined 1,991 patients were also compared.
It was discovered that mutations in the MSH3 gene, as well as 2 other genes – DHFR, and MTRNR2L2 – were associated with disease progression in both studies. MSH3, a DNA repair gene, has already previously been linked to changes in size of the HD mutation, and it was identified in the study that a variation in it encodes an amino acid change.
“This is an example of reverse translation: these novel findings we observed in people with HD support many years of basic laboratory work in cells and mice,” said the study’s co-senior researcher Dr Sarah Tabrizi of UCL. “Now that 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.”
“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 the study’s other co-senior researcher, Cardiff University professor Dr Lesley Jones.
Hensman Moss DJ, Pardinas AF, Langbehn D, et al. Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study. Lancet Neurol. 2017; DOI: 10.1016/S1474-4422(17)30161-8

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