Unlocking the future: Precision oligonucleotide therapy for targeted treatment of neurodegenerative disorders

Abstract

Neurodegenerative disorders are complex and devastating conditions of the central nervous system that profoundly impact quality of life. Given the limited treatment options available, there is a pressing need to develop novel therapeutic strategies. Oligonucleotides have emerged as key players in precision medicine for these disorders, but their potential is hindered by poor translocation across the blood-brain barrier. This review focuses on neurodegenerative disorders other than Alzheimer's and Parkinson's, which are widely reported in the literature, and aims to address the significant hurdles in oligonucleotide delivery for neurodegenerative diseases. It highlights recent advancements in CNS-targeting approaches, such as chemical conjugation, antibody-oligonucleotide conjugates, focused ultrasound, and viral and nanocarrier-based delivery systems. Each strategy's strengths and limitations are discussed, with potential solutions proposed for more effective treatments. Additionally, the review offers valuable insights into regulatory requirements and prospects for clinical translation, which are crucial for shaping the future of neurodegenerative therapies. By exploring these innovative approaches, the goal is to surmount challenges posed by the blood-brain barrier and develop more effective treatments, thereby enhancing the quality of life of the patients suffering from these debilitating conditions.

Keywords: Central nervous system; Nanotherapeutics; Neurodegenerative diseases; Oligonucleotide; Targeted drug delivery.