Researchers from Canada and France have identified a new gene, called TDP-43, which is responsible for a major fraction of ALS, (sporadic amyotrophic lateral sclerosis) cases or Lou Gehrig's disease.
ALS or Lou Gehrig's disease is an incurable neuromuscular disorder targeting motor neurons and causes paralysis and death within one to five years.
The study, led by Guy Rouleau of the Research Centre of the Centre hospitalier de l'Universite de Montreal (CRCHUM), was conducted on 200 human subjects with ALS.
After examining ALS patients from France and Quebec, the researchers observed a number of genetic mutations in the TDP-43 gene and hence they ascertained it to be responsible for up to 5 percent of the ALS patients.
The researchers build their study on a previous study in 1993 when they helped identify a gene "superoxide dismutase" as being responsible for the disease in 10 to 20 percent of all familial cases of ALS.
This study was taken as a foundation for the development of several mouse and rat models of ALS that closely resemble the motor neuron disorder found in ALS patients. These models have posed to be quite beneficial in studying molecular and cellular mechanisms of disease and to test ALS treatments.
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. Animal models over-expressing the mutations identified in this study will provide crucial insight into how TDP-43 aggregate and ultimately kill motor neurons," Nature quoted Dr. Rouleau, as saying.
"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, one of the co-investigators on the study.
The study is published in the current online edition of Nature Genetics.