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Post-Polio Health (ISSN 1066-5331)

Vol. 11, No. 2, Spring 1995

New Insights into ALS and the Impact on Post-Polio Research

Raymond P Roos, MD, Co-Director, Post-Polio Clinic, University of Chicago Medical Center, Chkago, Illinois

For over 10 years I have been the Director of a NIH-funded Program Project entitled "Motor Neuron Diseases," which focuses on amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease) and post-polio syndrome. One of the premises of this grant is that the mechanisms by which motor nerve cells die may be shared by varied diseases, i.e., we may learn more about post-polio syndrome by leaming more about ALS and vice versa. In this article I will discuss new knowledge about ALS and how it may impact on our understanding of post-polio syndrome.

When I took over as Director for the Program Project, I thought it most valuable to try to take advantage of the new powerful technologies in use in genetics in order to learn more about how motor neurons die. For this reason, I invited Dr. Teepu Siddique and colleagues (then at Duke University) to submit a research project in this Program Project in order to identify a "link" between susceptibility to familial ALS (FALS) and inheritance of a particular chromosome from an affected relative. As a result of his studies and many other collaborations, linkage was discovered and, about a year ago, the gene responsible for FALS was identified as superoxide dismutase-1 (SOD).

What does SOD do? SOD breaks down free radicals which are toxic products of cell metabolism. Free radicals have been implicated as a cause for cell death for years. The realization that mutations in SOD-1 lead to motor nerve cell death provided the first dear-cut evidence that free radicals could play a role in motor neuron degeneration. The actual mechanism by which motor nerve cells are specifically targeted is presently under intense investigation.

What are the implications of the discovery of SOD mutations in patients with FALS? Only 5-10% of cases of ALS are familial and only 20% of FALS cases are caused by SOD-1 mutations. Nevertheless, there is a strong feeling in the scientific community that the mechanisms of motor nerve death in sporadic ALS as well as other neurodegenerations may be similar to that in FALS. This same mechanism may also be responsible for the motor nerve cell death seen in post-poho progressive muscular atrophy.

What future directions are being pursued? One direction of great interest is the development of drugs that can counteract the effect of the mutant SOD. A great resource for the scientific community is the availability of experimental mice that carry the mutant human SOD gene and also develop an ALS-like syndrome. These mice are critically important in the development of new experimental treatments that can prevent the motor neuron degeneration. When new effective drugs are identified, they may be of use in post-polio patients as well.

These breakthroughs in ALS research are undoubtedly the most exciting ones that have occurred since this disease was first discovered over 100 years ago; I am optimistic that the new discoveries will also help us to understand a variety of neurodegenerative processes. These new insights are a testament to the powerful DNA recombinant technologies that are now available to investigate neurological diseases that have eluded our understanding. We hope that these new tools will also help clarify some of the mysteries of the post-polio syndrome and lead to their effective treatment.