Discovery of a key mechanism to halt the most common genetic form of ALS
Health
A specific molecular mechanism has been identified as the cause of the most frequent genetic forms of amyotrophic lateral sclerosis (ALS, also known as Charcot’s disease) and frontotemporal dementia (FTD). By neutralising the genetic abnormality shared by these two neurodegenerative disorders, a research team from the CNRS1 , in collaboration with scientists from Harvard University, has succeeded in preventing the premature degeneration of neurons, and motoneurons in several cellular and animal experimental models. The results will be published in Science on 05 February 2026.
- 1Working at the CNRS laboratory Architecture et réactivité de l’ARN.
In nearly half of familial cases of ALS and FTD, the same abnormality affects the C9ORF72 gene. This gene contains repetitive sequences located within an intron, a segment normally removed before protein synthesis. In patients with ALS or FTD, this elimination process is defective: the intron persists and is inappropriately translated, leading to the production of abnormal and toxic proteins that accumulate in neurons and motoneurons and drive their rapid degeneration.
The scientists precisely identified the starting point of this aberrant translation: a codon2 recognised by the ribosome3 as an atypical start signal. Targeted modification of this unique signal through the introduction of a single mutation is sufficient to completely abolishes the synthesis of the toxic proteins responsible for neuronal degeneration. This approach, validated in mouse models and in human ALS patient-derived motoneurons following CRISPR-Cas9–mediated genome editing, prevents disease development in mice and rescues the cellular lifespan to levels comparable with healthy cells. These findings pave the way for the development of new therapeutic strategies directly targeting the underlying cause of these disorders.
Bibliography
Blocking RAN translation without altering repeat RNAs rescues C9ORF72-related ALS/FTD phenotypes. Xin JIANG et al., Franck MARTIN and Clotilde LAGIER-TOURENNE, Science, 05 February 2026
