ABSTRACT
Amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, is the most common motor neuron disease. ALS is a late-onset rapidly deteriorating neurological disorder characterized by the selective death of motor neurons in the brain and spinal cord that innervate skeletal muscles, with clinical symptoms of progressive weakness, muscle wasting, and spasticity (1). The median survival with ALS is usually three years and the cause of death is respiratory failure, pneumonia, or cardiac arrhythmias. Scientific advancements have been made over the past several years to understand the Mendelian forms of ALS and other diseases of the motor neuron. The most significant advancement has been the identification of genes causing some forms of familial ALS (2,3), the spinal muscular atrophies (4,5), and frontotemporal dementia (6). The epidemiologic observation of specific patterns of familial aggregation in some individuals with motor neuron disease started the chain of events that led to the identification of the underlying genes. Despite exciting advances into understanding the molecular genetic basis of some Mendelian forms of the disease, however, the causes of sporadic (non-familial) ALS are still unknown, and the apparent selectivity for motor neurons remains unexplained.
