Treatment of amyotrophic lateral sclerosis: lessons learned from many failures

Amyotrophic lateral sclerosis (ALS) is one of the most complex neurodegenerative diseases, involving both cortical and spinal components of motor neuron circuitry and non-neuronal cells that support the motor neurons. There is no effective therapeutic for ALS, and compounds that have extended the lifespan of ALS mouse models have failed in clinical trials. This viewpoint discusses current information regarding the changing views about ALS and what the failures in clinical trials can teach us in the search for an effective treatment. Previous challenges and roadblocks in drug discovery for ALS are noted, and solutions to current limitations are discussed. Learning from the past and moving forward with a new mindset can translate into successful and effective treatment strategies in ALS and other related diseases.