Antisense Oligonucleotides as Precision Therapies for Neurodegenerative Diseases: A Narrative Review

Abstract

Context: Antisense oligonucleotides (antisense oligonucleotides (ASOs)) are emerging precision therapies that modulate RNA expression and have shown promise for neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. Evidence Acquisition: This narrative review summarizes key ASO mechanisms of action, major disease-related targets, delivery approaches, clinical progress, safety concerns, emerging technologies, approved ASO therapies, and ongoing clinical development relevant to neurodegeneration. Results: ASO-based therapies have shown increasing therapeutic potential across multiple neurodegenerative disorders, driven by advances in molecular targeting, delivery strategies, and clinical development. However, key safety concerns and translational barriers continue to limit their broader clinical application. Conclusions: ASO-based therapy represents a promising precision-medicine approach for neurodegenerative diseases. Further research should focus on overcoming translational barriers, improving delivery and safety, and advancing effective ASO therapies toward wider clinical adoption.