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

Figure 1

The motor columns of the spinal cord. The LMCs innervate the muscles of the upper and lower limbs, the MMC innervates axial musculature and the HMC and PGC are in the thoracic spinal cord and innervate the intercostal musculature and sympathetic ganglia respectively. LMC: Lateral motor column; MMC: Medial motor column; HMC: Hypaxial motor column; PGC: Preganglionic motor column; MNs: Motor neurons.