A Vitamin Treatment for Motor Neurone Disease

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by progressive degeneration of motoneurons within the brain and spinal cord. Both sporadic and genetic forms of the disease exist, with the former much more common, however their pathophysiology is complex and incompletely understood, with numerous mechanisms likely to contribute to disease development and progression. Due to the lack of effective treatments currently available, there is an urgent requirement for novel therapeutic approaches. It has been suggested that retinoids, a class of compounds derived from vitamin A, are able to modulate several of the pathways implicated in ALS. There is also growing evidence that retinoid signalling defects are involved in the pathogenesis of the disease. This implies that activation of retinoid signalling has a potential therapeutic role. Retinoid signalling is mediated by the retinoic acid receptor (RAR), which acts as a ligand-activated transcription factor to regulate the transcription of retinoic acid target genes. This review explores the major pathways thought to be involved in the pathophysiology of ALS and the mechanisms by which retinoids may modulate these pathways. To evaluate the potential therapeutic role of retinoid signalling activation, studies investigating the effects of retinoids in ALS are discussed. Currently, the majority of evidence suggests that retinoids act through the RAR to provide neuroprotection in ALS. However, outcomes vary according to the mechanism of drug delivery, indicating that although retinoids are a promising therapeutic strategy, the development of effective RAR-targeted drugs requires further research.