Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is an adult-onset progressive neuromuscular disease with no cure that affects nearly a quarter of a million people worldwide.
ALS symptoms typically appear between the ages of 55 to 75 with death, often due to respiratory failure, occurring within 3 to 5 years of symptom onset. At least 90% percent of cases are sporadic and have no clear associated risk factor or family history, whereas 5-10% of cases result form an inherited genetic mutation.
Genetic analysis of familial cases has identified mutations in over a dozen genes, including C9ORF72 (the most common mutation), SOD1, TARDBP, and FUS. Motor neuron loss is the cause of muscle weakness and inability to control movement in ALS.
Research seeking to understand the cause of motor neurons vulnerability indicates a variety of cellular defects, with intracellular aggregation of TDP-43 protein a hallmark of both sporadic and familial cases.