Treatment of Amyotrophic Lateral Sclerosis : From Genetics to Zebrafish


Université Pierre et Marie Curie
Université Pierre et Marie Curie


UMRS 1127 UMR 7225


Amyotrophic Lateral Sclerosis
motor neuron
multigenic interaction
chemical screening


TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis, Kabashi E, Valdmanis PN, Dion P, Spiegelman D, McConkey BJ, Vande Velde C, Bouchard JP, Lacomblez L, Pochigaeva K, Salachas F, Pradat PF, Camu W, Meininger V, Dupre N, Rouleau GA. Nat Genet. 2008 May;40(5):572-4. (Citations 318; IF 36.4)

FUS and TARDBP but not SOD1 interact in genetic models of ALS, Kabashi E, Bercier V, Lissouba A, Brustein E, Liao M, RouleauGA, Drapeau P PLoS Genetics 2011 Aug;7(8):e1002214. (IF 9.5)

In the swim of things: recent insights to neurogenetic disorders from zebrafish, Kabashi E, Champagne N, Brustein E, Drapeau P. Trends Genet. 2010 Aug;26:373-81. (Citations 3; IF 11.4

Gain and loss of function of ALS-related mutations of TARDBP (TDP-43) cause motor deficits in vivo, Kabashi E, Lin L, Tradewell M, Dion P, Bourgouin P, Rochefort D, Bel Hadj S, Durham H, Vande Velde C, Rouleau GA, Drapeau P. Hum Mol Genet 2010 Feb 15;19(4):671-83. (Citations 49; IF 8.1)

Oxidized/misfolded superoxide dismutase-1: the cause of all amyotrophic lateral sclerosis?, Kabashi E, Valdmanis PN, Dion P, Rouleau GA. Ann Neurol. 2007 Dec;62:553-9. (Citations 40; IF 10.8)

Fields of research

Neurological and psychiatric diseases

Research Theme

Our research team recently appointed at the Brain and Spinal Cord Institute will serve to close the gap between clinical and basic research in neuroscience. We will functionally characterize genetic variants for neurodegenerative diseases and develop models using these mutations. Further, we will use these models to identify and validate compounds with neuroprotective properties. Thus, our research will serve as a ring between clinical and basic research and we hope it will advance both these fields of neuroscience.

Revolutionary advances in human genetic studies allow rapid and efficient exome sequencing for patients affected by a variety of health-related disorders. However, a large number of data is generated that is difficult to analyze. Our team has used extensively zebrafish as a vertebrate model par excellence to characterize genes involved in ALS and other motor neuron diseases. Further, we will use the technological advances in zebrafish genetics, as we plan to generate transgenic lines for common genes involved in these disorders. These models will serve to better understand mechanisms of disease, identify partners of these mutant genes as well as to perform chemical screens for compounds that can rescue disease-related phenotype.

To perform these chemical screens, our group is developing tools to perform automated assays of zebrafish placed in multiwall plates where zebrafish larva are treated with specific chemical compounds. Video recording and analysis of the motor behavior is performed to identify compounds that significantly modulate swimming activity. These assays permit to identify compounds that could reverse neurodegenerative processes thus opening exciting avenues for clinical research. Compounds that are identified in these screens and validated in other models could propose efficient therapies for patients affected by these increasingly common neurological diseases.