Researchers identify a gene responsible for cases of Lou Gehrig’s

Montreal, QC – A team of Canadian and French researchers has identified a novel gene responsible for a significant fraction of ALS (sporadic amyotrophic lateral sclerosis) cases. ALS is commonly referred to as Lou Gehrig’s disease, an incurable neuromuscular disorder that affects motor neurons and leads to paralysis and death within one to five years.

Published on line March 30th in Nature Genetics, the study on 200 human subjects with ALS was led by Guy Rouleau, Edor Kabashi, Paul Valdmanis of the Research Centre of the Centre hospitalier de l’Universite de Montreal (CRCHUM). The team identified several genetic mutations in the TDP-43 gene by studying ALS patients from France and Quebec. They established TDP-43 as the gene responsible for up to 5% of the ALS patients.

The breakthrough is the result of teamwork with peers from the Waterloo and Laval universities in Canada and the Federation des maladies du systeme nerveux and the Institute of Biology (Unite de Neurologie Comportementale et Degenerative) in France.

Building on past studies In 1993, Dr Rouleau and his team also helped identify “superoxide dismutase” as the gene that causes the disease in 10 – 20% of all familial cases of ALS. This cornerstone study led to development of several mouse and rat models of ALS that closely resemble the motor neuron disorder observed in ALS patients. These models have been very useful to study molecular and cellular mechanisms of disease and to test treatments for ALS.

TDP-43’s normal function is to bind and splice RNA. Two years ago, a team from the University of Pennsylvania discovered TDP-43 in abnormal protein clumps, referred to as aggregates, in motor neurons of ALS patients. However, it was not certain whether TDP-43 causes motor neuron disease or is just a pathological marker.

“The identification of additional mutations in TDP-43 in other ALS patients will confirm that this gene is a prominent cause of this type of disorder,” said Dr Rouleau, director of the Sainte-Justine Hospital Research Centre. “Animal models over-expressing the mutations identified in this study will provide crucial insight into how TDP-43 aggregate and ultimately kill motor neurons.”

“This discovery is a step towards the development of therapies for people suffering from this terrible disease and possibly other neurodegenerative diseases,” said Dr Kabashi.