Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases

PURPOSE OF REVIEW This article reviews the clinical features, diagnostic approach, and treatments available for amyotrophic lateral sclerosis (ALS) and other motor neuron diseases. The article also provides an update on the genetics and pathophysiology of ALS.

RECENT FINDINGS ALS remains a clinical diagnosis without a unique biomarker. The areas of greatest progress include a large expansion in the number of genes associated with familial and sporadic ALS. The discovery of these genes, along with other work, has provided a deeper understanding of the mechanisms of motor neuron failure in ALS. Areas of particular interest include the role of transactive response DNA-binding protein 43 and other RNA-processing proteins in the development of disease.

SUMMARY ALS remains a relentlessly progressive disorder with an elusive core pathophysiology. The current mainstay of treatment remains symptom management and palliation, particularly in the setting of a multidisciplinary clinic. The future holds potential for targeted therapies based on an ever-evolving understanding of the pathophysiology of both familial and sporadic ALS.

Address correspondence to Dr Colin Quinn, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104, [email protected].

RELATIONSHIP DISCLOSURE: Dr Quinn serves on advisory boards for Acceleron Pharma, Inc, and Amylyx Pharmaceuticals and as a consultant for Amicus Therapeutics, Inc. Dr Quinn receives research/grant support from Acceleron Pharma, Inc; Amicus Therapeutics, Inc; and Amylyx Pharmaceuticals. Dr Elman serves on advisory boards for Biogen and Genentech, Inc, and receives publishing royalties from UpToDate, Inc.

UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE: Drs Quinn and Elman discuss the unlabeled/investigational use of anticholinergics, clonazepam, levetiracetam, mexiletine, mirtazapine, phenytoin, selective serotonin reuptake inhibitors, steroids, and tricyclic antidepressants for the treatment of amyotrophic lateral sclerosis and other motor neuron diseases.