Therapeutic Targeting of Proteostasis in Amyotrophic Lateral Sclerosis—a Systematic Review and Meta-Analysis of Preclinical Research

Background Amyotrophic lateral sclerosis (ALS) is a rapidly progressive fatal neurodegenerative condition. There are no effective treatments. The only globally licensed medication, that prolongs life by 2-3 months, was approved by the FDA in 1995. One reason for the absence of effective treatments i...

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Bibliographic Details
Published in:Frontiers in neuroscience 2020-05, Vol.14, p.511-511
Main Authors: Elliott, Elizabeth, Bailey, Olivia, Waldron, Fergal M., Hardingham, Giles E., Chandran, Siddharthan, Gregory, Jenna M.
Format: Article
Language:English
Subjects:
Amyotrophic lateral sclerosis
Autophagy
Dementia
Dementia disorders
Deoxyribonucleic acid
Disease
DNA
Frontotemporal dementia
Meta-analysis
motor neurone disease
Mutation
Neuroscience
Pathogenesis
Pathology
Pathophysiology
preclinical
Protein folding
Proteins
proteostasis
Spinal cord
Survival
Systematic review
Therapeutic targets
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Summary:Background Amyotrophic lateral sclerosis (ALS) is a rapidly progressive fatal neurodegenerative condition. There are no effective treatments. The only globally licensed medication, that prolongs life by 2-3 months, was approved by the FDA in 1995. One reason for the absence of effective treatments is disease heterogeneity noting that ALS is clinically heterogeneous and can be considered to exist on a neuropathological spectrum with frontotemporal dementia. Despite this significant clinical heterogeneity, protein misfolding has been identified as a unifying pathological feature in these cases. Based on this shared pathophysiology, we carried out a systematic review and meta-analysis to assess the therapeutic efficacy of compounds that specifically target protein misfolding in preclinical studies of both ALS and FTD. Methods Three databases: (i) Pubmed, (ii) MEDLINE and (iii) EMBASE were searched. All studies comparing the effect of treatments targeting protein misfolding in pre-clinical ALS or FTD models to a control group were retrieved. Results Systematic review identified 70 pre-clinical studies investigating the effects of therapies targeting protein misfolding on survival. Meta-analysis revealed that targeting protein misfolding did significantly improve survival compared to untreated controls (p
ISSN:1662-453X
1662-4548
1662-453X
DOI:10.3389/fnins.2020.00511