MSH3 Gene Mutations May Be Involved in Huntington’s Disease Progression, Study Finds

Joana Fernandes, PhD avatar

by Joana Fernandes, PhD |

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Mutations of the MSH3 gene may be associated with the progression of Huntington’s disease, according to a British study.

The gene could become a biomarker for the disease, and scientists may be able to develop Huntington’s therapies around it, the researchers from University College London and Wales’ Cardiff University said.

They published their study in the journal Lancet Neurology under the title “Identification of genetic variants associated with Huntington’s disease progression: a genome-wide association study.”

“We’ve identified a gene that could be a target for treating Huntington’s disease,” Dr. Davina Hensman Moss, the study’s first author, said in a news release. “While there’s currently no cure for the disease, we’re hopeful that our finding could be a step towards life-extending treatments,” said Moss, a professor at University College London’s Institute of Neurology.

Researchers looked at cognitive and movement symptoms in 218 patients in the TRACK-HD study who had Huntington’s-related genetic mutations. They compared the information with that of 1,773 participants in the European Huntington’s Disease Network REGISTRY study.

They also compared the symptoms and the disease’s progression with the genetic mutations the patients carried.

The team discovered that mutations in three genes – MSH3, DHFR, and MTRNR2L2 – were associated with disease progression in patients from the TRACK-HD study and, to a lesser extent, in patients from the REGISTRY study.

Researchers linked mutations of the MSH3 gene in particular to annual reductions in patients’ movement-capacity and total-functioning scores. The drops occurred in patients with the mutations regardless of how old they were when the disease started. The barometers the team used were the Unified Huntington’s Disease Rating Scale (UHDRS) Total Motor Score, which measures patients’ movement capacity, and UHDRS Total Functional Capacity Score.

“The strength of our finding implies that the variant we identified has a very large effect on HD [Huntington’s disease], 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 Dr. Lesley Jones, a Cardiff University professor who was the study’s co-senior researcher.

“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 Dr. Sarah Tabrizi of University College London, the study’s other co-senior researcher. “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.”