CRG: The messenger in Huntingon's disease

CRG: The messenger in Huntingon's disease

News from CRG

The research just published by a group of scientists from the CRG led by Eulàlia Martí, in cooperation with researchers from the UB and IDIBAPS, 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 November issue of The Journal of Clinical Investigation. Eulàlia Martí is the lead author, while Laura Rué and Mónica Bañez are its first authors.

Huntington’s disease is caused by the excessive repetition of a nucleotide triplet (CAG) in the Huntingtin gene. 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 Martí, “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,” states the researcher. As opposed to most other research groups, Eulàlia Martí’s team has sought to identify whether the problem resided in the messenger RNA – which would be the copy responsible for manufacturing the protein – or in the resulting protein. Prior work indicated that mRNA produced, in addition to defective protein, other damages. 

More information:
CRG website

Reference work:
Rué et al.: “Targeting CAG repeat RNAs reduces Huntington’s disease phenotype independently of huntingtin levels”, The Journal of Clinical Investigation. November 1, 2016; 126(11):4319–4330. doi:10.1172/JCI83185