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 in the current
online edition of Nature Genetics, the study on 200 human subjects with
ALS was led by Doctors Guy Rouleau, Edor Kabashi, Paul Valdmanis of the Research
Centre of the Centre hospitalier de l'Université de Montréal (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 five percent of the ALS patients.
The breakthrough is the result of
teamwork with peers from the Waterloo and Laval universities in Canada and the
Fédération des maladies du système nerveux and the Institute of Biology (Unité
de Neurologie Comportementale et Dégénérative) in France.
In 1993, Dr. Rouleau and his team also helped identify
"superoxide dismutase" as the gene that causes the disease in 10 to 20 percent
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
"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.
Article adapted by Medical News Today
from original press release.
Rouleau and Kabashi are financially supported by the Canadian Institutes of
Health Research (CIHR) and ALS Canada. Their research was also funded by the
Muscular Dystrophy Association and the ALS Association. For more information
about ALS, please visit http://www.als.ca/.
On the web:
About the CHUM
and the CRCHUM: http://www.chumtl.qc.ca/accueil.fr.html
Université de Montréal: http://www.umontreal.ca/english/index.html
This release is available in French.
Source: Nathalie Forgue
University of Montreal