"A FATAL MUSCLE DISEASE"

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, is a progressive fatal neuromuscular disease that attacks nerve cells and pathways in the brain and spinal cord. This debilitating disease affects several hundred Canadians each year. Motor neurons, among the largest of all nerve cells, reach from the brain to the spinal cord and from the spinal cord to muscles throughout the body. When a nerve cell dies, the ability of the brain to start and control muscle movement disappears. With all involuntary muscle action affected, ALS patients in the later stages are totally paralyzed, yet, throughout it all, the patients' mind remained unaffected.

LHSC neurologist Dr. Michael Strong has spent the last six years working with other scientists to experimentally recreate the disease in New Zealand white rabbits in an effort to better understand what happens to the motor neurons. Having successfully accomplished this, these scientists have now been able to stop the progression of the disease and indeed reverse the affects of the disease in these rabbits.

"What this research has shown us is that what we thought was an untreatable disease may be treatable. This is because we believe we can isolate the protein in nerve cells which is affected in ALS," says Dr. Strong, adding that approximately 70 per cent of ALS patients have a modification of the neurofilament protein.

Specifically, this research involved injecting aluminum chloride into the brains of the rabbits. The innoculations occurred at intervals of every 28 days for 10 months. During this time, a syndrome of progressive motor neuron dysfunction developed. Aluminum-inoculated rabbits gradually developed an increasing degree of motor dysfunction characterized initially by splaying of the hindlimbs and culminating in exaggerated reflexes in all limbs, gait abnormalities, paraspinal hypotonia and impaired tonic immobility responses. The scientists then examined how the aluminum modified the proteins in the cells themselves. It was also observed that the rabbits with the most pronounced clinical signs and symptoms had the greatest degree of change in the important protein in the neurons, the neurofilament.

Complete recovery was observed in rabbits who received innoculations only until day 51, although signs of motor system dysfunction were minimal at this time interval. Clinical recovery was more pronounced in the rabbits who had no more injections after day 107. And, in spite of the severity of clinical deficits by day 156, with two of the three rabbits very ill at this interval, recovery ensued with only hindlimb weakness and abnormal reflexes seen.

"If we can understand why this modification occurred in an animal model, then perhaps we will understand what happens in humans. . . .but that's still a long way away. The question is whether the modification in the neuron proteins is the primary event. It may be the initiating cause comes in, injures the cells, and it's the response to these injuries that is the problem," cautions Dr. Strong.

"This research does, however, provide a valuable experimental system for enhancing our understanding of the cause of the development of neurofilamentous inclusion formation in this disease, and the role, if any, that this might play in the bringing about the death of the motor neurons." An understanding of the fundamental process is key to any strategy for treatment or prevention.

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