Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration of both upper motor neurons (in the brain cortex) and lower motor neurons (in the spinal cord), leading to weakness and paralysis of voluntary muscles. Despite the progressive muscle weakness and eventual paralysis, cognition and sensation are typically preserved. The disease typically begins with focal weakness—often in one limb or in speech/swallowing muscles—and progresses to generalized weakness. Fasciculations (muscle twitching visible under the skin) are characteristic. The disease ultimately leads to respiratory failure requiring mechanical ventilation. ALS is relentlessly progressive and currently has no cure, though several disease-modifying therapies can slow progression and prolong survival. Two drugs (riluzole and edaravone) have FDA approval for slowing disease progression. Approximately 10% of ALS is familial (genetic), while 90% is sporadic. Recent research has identified multiple genetic mutations and molecular pathways involved in neurodegeneration.