Quo vadis motor neuron disease?

Abstract

Motor neuron disease (MND), also known as amyotrophic lateral sclerosis, is a relentlessly progressive neurodegenerative condition that is invariably fatal, usually within 3 to 5 years of diagnosis. The aetio-pathogenesis of MND remains unresolved and no effective treatments exist. The only Food and Drug Administration approved disease modifying therapy is riluzole, a glutamate antagonist, which prolongs survival by up to 3 mo. Current management is largely symptomatic/supportive. There is therefore a desperate and unmet clinical need for discovery of disease mechanisms to guide novel therapeutic strategy. In this review, we start by introducing the organizational anatomy of the motor system, before providing a clinical overview of its dysfunction specifically in MND. We then summarize insights gained from pathological, genetic and animal models and conclude by speculating on optimal strategies to drive the step change in discovery, which is so desperately needed in this arena.

Keywords: Motor neuron disease; Amyotrophic lateral sclerosis; Neurodegeneration; Disease models

Core tip: Motor neuron disease (MND) is a fatal neurodegenerative disorder with no known cure. Here we discuss the organization of the motor system and the clinical presentation of MND. We detail the diagnostic criteria for MND including electrophysiological studies and potential future diagnostic markers of disease. We discuss the staging of disease progression in MND. We then provide an overview of disease management and end with insights into molecular pathogenesis of the disease and the use of disease models.