Understanding and managing metabolic dysfunction in Amyotrophic Lateral Sclerosis.

INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is a fatal motor neuron disease that leads to death after a median survival of 36 months. The development of an effective treatment has proven to be extremely difficult due to the inadequate understanding of the pathogenesis of ALS. Energy metabolism is thoroughly involved in the disease based on the discoveries of hypermetabolism, lipid/glucose metabolism, the tricarboxylic acid (TCA) cycle, and mitochondrial impairment. AREA COVERED: Many perturbed metabolites within these processes have been identified as promising therapeutic targets. However, the therapeutic strategies targeting these pathways have failed to produce clinically significant results. The authors present in this review the metabolic disturbances observed in ALS and the derived-therapeutics. EXPERT OPINION: The authors suggest that this is due to the insufficient knowledge of the relationship between the metabolic targets and the type of ALS of the patient, depending on genetic and environmental factors. We must improve our understanding of the pathological mechanisms and pay attention to the subtle hidden effects of changing diet, for example, and to use this strategy in addition to other drugs or to use metabolism status to determine subgroups of patients.

Plasma creatinine and amyotrophic lateral sclerosis prognosis: a systematic review and meta-analysis.

Background: Plasma creatinine has been described as a prognostic biomarker for Amyotrophic Lateral Sclerosis (ALS), but with conflicting results in the literature. We performed a systematic review followed by a meta-analysis to address this question. Methods: We performed a systematic review of Pubmed, Embase and Cochrane databases and retrieved 14 distinct cohorts (19 studies) reporting results regarding the relationship between plasma creatinine and a clinical marker for ALS progression, notably ALSFRS (ALS Functional Rating Scale) and survival. Results: For baseline plasma creatinine, mortality risk was 28% lower when creatinine was higher than 88.4 µmol/L (hazard ratio (HR): 0.72; 95% confidence interval (CI): 0.58 to 0.88; p = 0.0003) and was 25% lower if creatinine was above versus below the median (HR: 0.75; 95% CI: 0.63 to 0.89; p = 0.0008). We found a significant positive correlation between plasma creatinine at baseline and functional score, and between creatinine decline and functional score decline (p < 0.0001 for both); but a negative correlation between plasma creatinine and functional score decline (p = 0.033). The overall quality of the studies was low mainly due to potential attrition bias, and several studies did not report analyzable results raising concern regarding a potential reporting bias. Conclusions: Plasma creatinine seems to be a promising prognostic biomarker for ALS. However, new studies with sound methodology and standardized criteria for the evaluation of ALS progression should be conducted to validate plasma creatinine as a clinical biomarker for ALS prognosis.