Version 1
: Received: 28 September 2024 / Approved: 30 September 2024 / Online: 30 September 2024 (14:42:20 CEST)
How to cite:
Moriyama, H.; Yokota, T. Recent Progress of Antisense Oligonucleotide Therapy for Superoxide Dismutase 1-mutated Amyotrophic Lateral Sclerosis: Focus on Tofersen. Preprints2024, 2024092440. https://doi.org/10.20944/preprints202409.2440.v1
Moriyama, H.; Yokota, T. Recent Progress of Antisense Oligonucleotide Therapy for Superoxide Dismutase 1-mutated Amyotrophic Lateral Sclerosis: Focus on Tofersen. Preprints 2024, 2024092440. https://doi.org/10.20944/preprints202409.2440.v1
Moriyama, H.; Yokota, T. Recent Progress of Antisense Oligonucleotide Therapy for Superoxide Dismutase 1-mutated Amyotrophic Lateral Sclerosis: Focus on Tofersen. Preprints2024, 2024092440. https://doi.org/10.20944/preprints202409.2440.v1
APA Style
Moriyama, H., & Yokota, T. (2024). Recent Progress of Antisense Oligonucleotide Therapy for Superoxide Dismutase 1-mutated Amyotrophic Lateral Sclerosis: Focus on Tofersen. Preprints. https://doi.org/10.20944/preprints202409.2440.v1
Chicago/Turabian Style
Moriyama, H. and Toshifumi Yokota. 2024 "Recent Progress of Antisense Oligonucleotide Therapy for Superoxide Dismutase 1-mutated Amyotrophic Lateral Sclerosis: Focus on Tofersen" Preprints. https://doi.org/10.20944/preprints202409.2440.v1
Abstract
Amyotrophic lateral sclerosis (ALS) is a refractory neurodegenerative disease characterized by the de-generation and loss of motor neurons, leading to death within five years of onset. There have been few effective treatments, making the development of robust therapies an urgent challenge. Genetic mutations have been identified as contributors to ALS, with mutations in superoxide dismutase 1 (SOD1), which neutralizes the harmful reactive oxygen species superoxide, accounting for approximately 2% of all ALS cases. To counteract the toxic gain of function caused by SOD1 mutations, therapeutic strategies aimed at suppressing SOD1 gene expression have shown promise. Antisense oligonucleotide (ASO) is an arti-ficially synthesized short single-stranded DNA/RNA molecule that binds to target RNA to alter gene expression, representing a next-generation therapeutic approach. In 2023, tofersen became the first ASO drug approved by the FDA for ALS. Administered intrathecally, tofersen specifically binds to SOD1 mRNA, inhibiting the production of toxic SOD1 protein, thereby improving biomarkers of ALS. The long-term efficacy and safety of tofersen require further validation, and the development of more opti-mized treatment protocols is essential. A series of studies and therapeutic developments related to SOD1 mutations have advanced the understanding of ALS pathophysiology and significantly contributed to treatment strategies for central nervous system disorders. This review focuses on the overview of SOD1 mutations and the development process of tofersen, aiming to deepen the understanding of advancements in ALS research and discuss future challenges and directions for ASO therapy.
Keywords
amyotrophic lateral sclerosis (ALS); superoxide dismutase 1 (SOD1); antisense oligonucleotide (ASO); tofersen; central nervous system
Subject
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
