Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis

Kiterie M E Faller; Helena Chaytow; Thomas H Gillingwater

doi:10.1038/s41582-024-01049-4

Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis

Nat Rev Neurol. 2025 Jan 2. doi: 10.1038/s41582-024-01049-4. Online ahead of print.

Authors

Kiterie M E Faller^#^{1

2

3}, Helena Chaytow^#^{1

2}, Thomas H Gillingwater^{4

5}

Affiliations

¹ Edinburgh Medical School, Biomedical Sciences, University of Edinburgh, Edinburgh, UK.
² Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh, UK.
³ Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK.
⁴ Edinburgh Medical School, Biomedical Sciences, University of Edinburgh, Edinburgh, UK. t.gillingwater@ed.ac.uk.
⁵ Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh, UK. t.gillingwater@ed.ac.uk.

^# Contributed equally.

PMID: 39743546
DOI: 10.1038/s41582-024-01049-4

Abstract

The motor neuron disease amyotrophic lateral sclerosis (ALS) is a devastating condition with limited treatment options. The past few years have witnessed a ramping up of translational ALS research, offering the prospect of disease-modifying therapies. Although breakthroughs using gene-targeted approaches have shown potential to treat patients with specific disease-causing mutations, the applicability of such therapies remains restricted to a minority of individuals. Therapies targeting more general mechanisms that underlie motor neuron pathology in ALS are therefore of considerable interest. ALS pathology is associated with disruption to a complex array of key cellular pathways, including RNA processing, proteostasis, metabolism and inflammation. This Review details attempts to restore cellular homeostasis by targeting these pathways in order to develop effective, broadly-applicable ALS therapeutics.

Publication types

Review