Mansour Heba M, El-Khatib Aiman S
Central Administration of Biologicals, Innovative Products, and Clinical Studies, Egyptian Drug Authority, EDA, Giza, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Eur J Pharmacol. 2025 Jul 5;998:177529. doi: 10.1016/j.ejphar.2025.177529. Epub 2025 Mar 19.
Antisense oligonucleotides (ASOs) specifically bind to target RNA sequences and regulate protein expression through various mechanisms. ASOs are a promising therapeutic approach for treating neurodegenerative diseases. The ASO field is a growing area of drug development that focuses on targeting the root cause of diseases at the RNA level, providing a promising alternative to therapies that target downstream processes. Addressing challenges related to off-target effects and inadequate biological activity is essential to successfully develop ASO-based therapies. Researchers have investigated various chemical modifications and delivery strategies to overcome these challenges. This review discusses oligonucleotide-based therapies, particularly ASOs. We discuss the chemical modifications and mechanisms of action of ASOs. Additionally, we recap the results of preclinical and clinical studies testing different ASOs in various neurodegenerative disorders, including spinal muscular atrophy, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease. In conclusion, ASO drugs show promise as a therapeutic option for treating neurodegenerative diseases.
反义寡核苷酸（ASO）特异性结合靶RNA序列，并通过多种机制调节蛋白质表达。ASO是治疗神经退行性疾病的一种有前景的治疗方法。ASO领域是药物开发中一个不断发展的领域，专注于在RNA水平上针对疾病的根本原因，为针对下游过程的疗法提供了一种有前景的替代方案。解决与脱靶效应和生物活性不足相关的挑战对于成功开发基于ASO的疗法至关重要。研究人员已经研究了各种化学修饰和递送策略来克服这些挑战。本综述讨论基于寡核苷酸的疗法，特别是ASO。我们讨论了ASO的化学修饰和作用机制。此外，我们总结了在各种神经退行性疾病（包括脊髓性肌萎缩症、亨廷顿舞蹈症、肌萎缩侧索硬化症、阿尔茨海默病和帕金森病）中测试不同ASO的临床前和临床研究结果。总之，ASO药物作为治疗神经退行性疾病的一种治疗选择显示出前景。
