Amyotrophic Lateral Sclerosis

Abstract

This chapter was originally intended to cover both amyotrophic lateral sclerosis (ALS) and multiple sclerosis, but we will concentrate on ALS. There are nonetheless several reports from the literature that ionotropic glutamate receptor antagonists have beneficial effects in animal models of multiple sclerosis (1,7,14,58,71,109) and this could develop into a very promising therapeutic area in the future. The interested reader is referred to the following review (59). However, the evidence for involvement of disturbances in the glutamatergic system in ALS is already convincing and has led to the use of the glutamate release inhibitor riluzole in the treatment of this disease. As such, we felt that a book on the therapeutic potential of ionotropic glutamate receptor antagonists and modulators would be incomplete without a chapter on this disease. RATIONALEALS, commonly called Lou Gehrig's disease, is a devastating neurological disorder characterized by selective upper and lower somatic, but not autonomic, motor neurone degeneration leading to paralysis and eventually death. The diagnosis of ALS requires the presence of both upper and lower motor neurone degeneration and progressive motor dysfunction. ALS occurs in 1 to 2.5 cases per 100,000 population, affects more men than women, and is most commonly diagnosed in middle age. Other functions such as intellectual abilities and sensory perception are preserved. At advanced stages patients become completely disabled, often requiring ventilatory support and feeding by gas-

Efficacy of thalidomide for the treatment of amyotrophic lateral sclerosis: A phase II open label clinical trial

“…There are most certainly variations in the pathophysiology among sporadic ALS (SALS), non-mutant SODl-related FALS, and mutant SODl-related FALS diseases. A lack of response to therapeutic intervention for ALS with any treatment may also be related to the fact that the disease is very advanced by the time a diagnosis is made and the MN are markedly compromised, suggested both by previous histological (30-32) and electrodiagnostic (33-35) assessment.…”

Efficacy of thalidomide for the treatment of amyotrophic lateral sclerosis: A phase II open label clinical trial

“…There are most certainly variations in the pathophysiology among sporadic ALS (SALS), non-mutant SODl-related FALS, and mutant SODl-related FALS diseases. A lack of response to therapeutic intervention for ALS with any treatment may also be related to the fact that the disease is very advanced by the time a diagnosis is made and the MN are markedly compromised, suggested both by previous histological (30-32) and electrodiagnostic (33-35) assessment.…”

Efficacy of thalidomide for the treatment of amyotrophic lateral sclerosis: A phase II open label clinical trial

“…There are most certainly variations in the pathophysiology among sporadic ALS (SALS), non-mutant SODl-related FALS, and mutant SODl-related FALS diseases. A lack of response to therapeutic intervention for ALS with any treatment may also be related to the fact that the disease is very advanced by the time a diagnosis is made and the MN are markedly compromised, suggested both by previous histological (30-32) and electrodiagnostic (33-35) assessment.…”

Efficacy of thalidomide for the treatment of amyotrophic lateral sclerosis: A phase II open label clinical trial

“…There are most certainly variations in the pathophysiology among sporadic ALS (SALS), non-mutant SODl-related FALS, and mutant SODl-related FALS diseases. A lack of response to therapeutic intervention for ALS with any treatment may also be related to the fact that the disease is very advanced by the time a diagnosis is made and the MN are markedly compromised, suggested both by previous histological (30-32) and electrodiagnostic (33-35) assessment.…”