Amyotrophic Lateral Sclerosis: The Role of Inflammation and Its Clinical Impact

Some 100 researchers meet at the CHUL (CHUQ) Research Centre for the Fondation André-Delambre’s 2nd Symposium (September 8 and 9, 2006)

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease and Maladie de Charcot, is a terrible, incurable disease characterized by a progressive loss of motor neurons, which leads to progressive paralysis and usually death caused by respiratory failure several years after diagnosis. On September 8 and 9, the CHUL (CHUQ) Research Centre hosted the Fondation André-Delambre’s 2nd Annual Symposium on ALS. Some 100 researchers and clinicians from a number of countries participated in the symposium to discuss the causes of ALS and, especially, the role of inflammation in the disease and its clinical impact. Professor Jean-Pierre Julien, the Symposium’s organizer, invited 22 internationally renowned speakers from many cities (Atlanta, Baltimore, Boston, Houston, Leuven, London ON, London, Madison, Milan, Montréal, New York, Philadelphia, Québec, San Diego, Toronto, Vancouver).

The theme of the Symposium was the role of inflammation in ALS. Thus, a number of the Symposium speakers presented data showing that the loss of motor neurons in ALS is not simply a problem intrinsic to the motor neurons, but also involves toxicity arising from the entourage of the motor neurons. Recent discoveries presented by Dr. Appel (Houston), Dr. Cleveland (San Diego), Dr. Robberecht (Leuven), Dr. Shaw (UBC) and Dr. Julien (Laval) suggest that the glial cells in the motor neurons’ entourage could play a part in the degeneration of motor neurons. One of the hypotheses postulates that the motor neurons are prey to a harmful inflammatory process involving the excessive production of proinflammatory molecules, oxygen radicals and glutamate by the glial cells. Nevertheless, there was debate over whether the inflammation was harmful or protective.

It should be noted that several speakers presented results that suggest a protective role for some immune response processes, not only in ALS (J.-P. Julien – Laval), but also in cerebral ischaemia (J. Kriz – Laval), Alzheimer’s disease (S. Rivest – Laval) and Parkinson disease (S. Przedborski – Columbia NY).

The Symposium began with a summary by Dr. Robert Brown (Harvard) of the genetic causes of ALS. A major breakthrough was made in 1993 with the discovery of mutations in the gene for superoxyde dismutase (SOD1) in 20% of familial cases of the disease. Since this discovery, many of the world’s research teams have been trying to understand how SOD mutations can cause selective loss of motor neurons. Several speeches were about the toxicity aspects of mutant SOD1, which can affect cell-death signalling pathways (C. Bendotti – Milan), the chaperone system and protein degradation (H. Durham – McGill), the axon cytoskeleton (C. Miller – London, J. Robertson – Toronto, M. Strong – UWO, J. Glass – Emery/Atlanta) and protein aggregation (N. Cashman – Vancouver).

Some presentations were about new therapeutic approaches, such as gene therapy, trophic factors and stem cells (J. Rothstein – Johns Hopkins, R. Kalb – Pennsylvania, D. Lambrechts – Leuven, C. Svendsen – Wisconsin). Lastly, after two days of intense debate, the Symposium ended with presentations on medications that are under development, the validity of mouse models and clinical tests currently in progress on patients with ALS (A. Genge – McGill, M. Cudkowicz – Harvard). Riluzole, a compound that prolongs the life of ALS patients by three months, is today the only drug for treating this disease. In recent years, several pharmaceutical products failed in clinical trials on ALS patients. There is hope, however, since a number of other compounds are currently undergoing Phase 3 clinical trials. The results of these tests will be known in another two years.   

The Fondation André-Delambre’s 2nd Symposium was a success, not only because of the number of participants but especially because of the high scientific level of the discussions, the enthusiasm of the participants and the quantity of previously unpublished results presented by the speakers. What makes this annual Symposium stand out is the friendly atmosphere, which is conducive to dialogue among participants. Moreover, an important positive effect of the Symposium was the establishment of several new cooperative ventures among participating researchers. We hope that these cooperative projects will allow research to move forward more quickly and get closer to the objective of finding a therapeutic approach that can stop this terrible illness.