Antioxidant therapy in inborn metabolic diseases

Abstract

Oxidative stress contributes to the pathophysiology of several inherited metabolic diseases (IMDs). The quality and extent of clinical evidence for the use of antioxidant therapies in IMDs have yet to be ascertained. Despite frequent clinical use, robust evidence from large-scale trials is limited. The strongest support comes from studies on idebenone in Leber's hereditary optic neuropathy, showing improvements in visual outcomes. For other antioxidants and conditions, evidence is mixed or constrained by small sample sizes and short trial durations. Coenzyme Q10 in mitochondrial diseases, vitamin E in lipid disorders, and N-acetylcysteine in various IMDs have shown some promise, but evidence is heterogeneous. Challenges include optimizing dosing, dissecting oxidative stress mechanisms across disorders, and overcoming pharmacokinetic limitations. High-grade evidence exists for the clinical efficacy of N-acetyl-L-leucine for both Niemann Pick type C disease and other lysosomal storage diseases, though its potential antioxidant effect is indirect. This review highlights the need for larger trials with standardized, clinically relevant outcomes. Future research should explore oxidative stress mechanisms, targeted therapies, and combination approaches. While antioxidants hold potential, evidence remains limited, warranting cautious use and further investigation to define their role in these rare but cumulatively impactful disorders.

Synopsis

This review finds limited robust evidence for antioxidant therapies in inherited metabolic diseases, highlighting the need for larger trials and more targeted approaches.