Amyotrophic lateral sclerosis (ALS) is a devastating disease of the motor nervous system. While most cases are sporadic, approximately 5% to 10% of cases are familial and result from mutation in 1 of more than 25 known ALS genes. These genes span a surprisingly broad range of molecular functions, including RNA metabolism, oxidative stress, axonal transport, autophagy, excitability, and immunity. One of the great mysteries in the field is that motor neuron disease results as a convergent phenotype from mutations in this diverse group of genes. Understanding this puzzle is likely key to optimizing both clinical trials and patient treatment because different drugs may ultimately be necessary for targeting specific disease variants.
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