Rosa Rademakers and Bryan Traynor independently solved a decades-old mystery in neurodegenerative disease by discovering the most common genetic cause of both amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, and frontotemporal dementia (FTD), the second leading cause of early-onset dementia. Through multi-year, international collaborations, they collected large-scale data from families where both ALS and FTD appeared together; and through painstaking genetic analysis they zeroed in on a key genetic trigger for both diseases. In 2011, their labs simultaneously identified a mutation in the C9orf72 gene. It is an expansion mutation – a repeat of the same six-letter sequence of DNA, occurring hundreds to thousands of times in affected individuals.

The discovery represents a landmark moment in the study of these diseases. This single mutation explains about a third of familial cases of both diseases in European populations, as well as more than 5 percent of cases in patients with no family history of the diseases. It sheds light on the disease mechanisms, pointing in particular to multiple effects of toxic RNA and proteins in brain cells. It has established ALS and FTD – previously considered two largely separate disorders – on a disease spectrum, sharing risk factors and molecular causes. And perhaps most significantly it has enabled genetic testing for affected families, and opened new pathways for the development of treatments for these currently incurable diseases – including at least two therapies currently undergoing clinical trials. While ALS and FTD remain incurable, thanks to the C9orf72 discovery they are now conditions with plausible molecular causes and promising therapeutic targets.