Amyotrophic lateral sclerosis (ALS) is the most common disease of the motor neurons in the central nervous system in humans. Progressive loss of motor neurons leads to loss of motor activity and therefore, causes atrophy of the skeletal muscles. The loss of function of the muscles of the thoracic cavity ultimately leads to respiratory failure and death. Riluzole which is a glutamate inhibitor and during the period of respiratory failure, mechanically supported ventilation are the only means for prolonging lives of patients with ALS. ALS commonly occurs in a sporadic form. However, in 15% of cases, ALS occurs as a familial disease. The cause of this form of the disease has been attributed to a dominant mis-sense mutation of the gene encoding the copper/zinc superoxide dismutase (Cu/Zn-SOD; EC.1.15.1.1). The mutation results in the instability of the enzyme and therefore leads to its reduced activity in patients that carry the mutation. Transgenic mice which express the mutant Cu/Zn-SOD exhibit a paralytic, dominantly inherited, disorder that mimics the clinical and pathological features of the familial form of ALS in humans. Therefore, these mice are being used as a model for the human disease.

Bcl-2 is reduced in the motor neurons in the spinal cord of the ALS patients. Inspired by the fact that Bcl-2 prevents apoptosis and its overexpression in transgenic mice leads to a reduced volume of brain infarction in a model of ishemia, and prevents neuronal body loss in a model of progressive motoneuropathy, Kostic et al overexpressed the Bcl-2 in transgenic mice that expressed the mutated form of Cu/Zn-SOD. This overexpression delayed the onset of the disease, reduced the degeneration of motor neurons in the spinal cord and prolonged survival of these mice. This overexpression, however, did not alter the duration of the disease. Based on these findings, Kostic et al concluded that the anti-apoptotic therapy may only be used in ALS patients only if such treatment can be instituted before the onset of the symptoms.

REFERENCES:

Kostic V, Jackson-Lewis V, Bilbao F, Dubois-Dauphin M, Przedborski S: Bcl-2: Prolonging life in a transgenic model of familial amyotrophic lateral sclerosis. Science, 277, 559-562, 1997

RESOURCES:

ALS Digest Internet
ALS Interest Group Archive
Neurosciences on the Internet
RILUTEK®
RILUTEK® Now Available by Prescription for ALS
ALERT - RILUTEK® (Riluzole)
ADA Accessibility Guidelines
CenterWatch Clinical Trials Listing Service
Baylor College of Medicine ALS Clinic
Americans with Disabilities Act
The ALS Source
ALS Resources
The ALS Association (ALSA)
Apple's Mac Access Passport Online
ALS Page
Tube Feeding at Home

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