Newly published research has brought to light new information on the molecular mechanisms that cause Huntington’s disease, and defines new pathways to therapy discovery. The results of the study are published in The Journal of Clinical Investigation.

Huntington’s disease is caused by the excessive repetition of a nucleotide triplet (CAG) in the Huntingtin gene. The number of CAG repetitions varies from person to person. Healthy individuals can have up to 36 repetitions. Nevertheless, as of 36 repetitions, Huntington’s disease develops. The direct consequence of this excess of repetitions is the synthesis of a mutated protein–different from what would be obtained without the additional CAG repetitions–which has been considered the main cause of the disease for the past 20 years.

“What we have observed in our study is that the mutated fragment acting as a conveyor–the so-called messenger RNA–is key in the pathogenesis,” says Dr. Eulàlia Martí, one of the lead authors of the paper.  “The research on this disease being done by most groups around the world seeking new therapeutic strategies focuses on trying to prevent expression of the mutated protein. Our work suggests that blocking the activity of messenger RNA (the ‘conveyor’), would be enough to revert the alterations associated with Huntington’s disease. We hope this will contribute to improving the strategies in place to find a cure.”

Paper: “Targeting CAG repeat RNAs reduces Huntington’s disease phenotype independently of huntingtin levels”
Reprinted from materials provided by the Centre for Genomic Regulation.

January 20, 2017