Targeting mitochondrial dysfunction in amyotrophic lateral sclerosis: a systematic review and meta-analysis

Area of Science:

• Neuroscience
• Mitochondrial Biology
• Drug Discovery

Background:

• Mitochondrial dysfunction is implicated in amyotrophic lateral sclerosis (ALS) pathogenesis.
• Targeting mitochondria represents a potential therapeutic strategy for ALS.

Purpose of the Study:

• To systematically review and assess the efficacy of targeting mitochondria in preclinical amyotrophic lateral sclerosis (ALS) models.
• To evaluate the impact of intervention timing on survival benefits.

Main Methods:

• Systematic review of preclinical studies on targeting mitochondria in ALS models.
• Meta-analysis of survival data from 76 included studies.
• Assessment of intervention timing, study quality, and publication bias.

Main Results:

• Targeting mitochondrial dysfunction significantly improved survival in ALS preclinical models (P<0.00001).
• Greatest survival benefits were observed with interventions administered before disease onset.
• Publication bias was identified, with an outlier study overestimating the effect size.

Conclusions:

• Targeting mitochondrial dysfunction shows promise for prolonging survival in amyotrophic lateral sclerosis (ALS), especially with early intervention.
• Further research is needed, particularly on models beyond superoxide dismutase 1 and TAR DNA binding protein 43 proteinopathy.
• Mitochondrial-targeted therapies warrant further investigation for ALS treatment.