Team science unravels the link between ALS and FTD

2011

Challenge

Amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease) is a fatal neurodegenerative disorder that leads to progressive paralysis and respiratory failure Amyotrophic Lateral Sclerosis (ALS) Fact Sheet. Frontotemporal dementia (FTD) is the most common form of dementia in the under-65 population  A Review for Primary Care Physicians. Researchers have long suspected an overlap between the two diseases, but the molecular and genetic basis of this intersection was unknown.

Advance

IRP researcher Bryan J. Traynor, M.D., Ph.D., brought historically competitive research groups together to focus their efforts on identifying the underlying genetic cause of ALS and FTD. The new international consortium discovered that an insertion mutation disrupting the C9ORF72 gene is the most common genetic cause of both ALS and FTD identified to date, accounting for 40 percent of all familial cases of ALS and FTD in European and North American populations.

Impact

Discovery of this mutation changed scientific understanding of neurodegenerative diseases, influencing the diagnosis and investigation of ALS and FTD and, for the first time, mechanistically linking the two disorders. It also suggested a therapeutic target for gene therapy, with further research ongoing.

Publications

Renton AE, Majounie E, Waite A, Simón-Sánchez J, Rollinson S, Gibbs JR, Schymick JC, Laaksovirta H, van Swieten JC, Myllykangas L, Kalimo H, Paetau A, Abramzon Y, Remes AM, Kaganovich A, Scholz SW, Duckworth J, Ding J, Harmer DW, Hernandez DG, Johnson JO, Mok K, Ryten M, Trabzuni D, Guerreiro RJ, Orrell RW, Neal J, Murray A, Pearson J, Jansen IE, Sondervan D, Seelaar H, Blake D, Young K, Halliwell N, Callister JB, Toulson G, Richardson A, Gerhard A, Snowden J, Mann D, Neary D, Nalls MA, Peuralinna T, Jansson L, Isoviita VM, Kaivorinne AL, Hölttä-Vuori M, Ikonen E, Sulkava R, Benatar M, Wuu J, Chiò A, Restagno G, Borghero G, Sabatelli M; ITALSGEN Consortium, Heckerman D, Rogaeva E, Zinman L, Rothstein JD, Sendtner M, Drepper C, Eichler EE, Alkan C, Abdullaev Z, Pack SD, Dutra A, Pak E, Hardy J, Singleton A, Williams NM, Heutink P, Pickering-Brown S, Morris HR, Tienari PJ, Traynor BJ. (2011). A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron. 72(2), 257-68.