ArticleThe Journal of clinical investigation2018
Antisense oligonucleotides extend survival and reverse decrement in muscle response in ALS models.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
169 citing papers in PubMed, 262 citations in OpenAlex.
- Antisense oligonucleotide treatment following viral delivery of artificial SOD1-targeting miRNA shows improved efficacy in SOD1-G93A mice.Molecular therapy. Advances · 2026Article
- To scramble or not: Steric blocking 2'-MOE/PS control antisense oligonucleotides across cellular models.Molecular therapy. Nucleic acids · 2026Article
- Neural Stem Cell-Derived Extracellular Vesicles Improve CNS Delivery and Therapeutic Efficacy of Antisense Oligonucleotide in Amyotrophic Lateral Sclerosis.Journal of extracellular vesicles · 2026Article
- Genetic contributions to mitochondrial dysfunction in amyotrophic lateral sclerosis etiology.HGG advances · 2026Article
- Oligonucleotide-siRNA conjugate for SOD1 amyotrophic lateral sclerosis: a phase 1 trial.Nature medicine · 2026Article
- Intravenous administration of an engineered AAV9-gene-silencing vector suppresses human SOD1 and extends survival in an ALS mouse model.Nature communications · 2026Article
- Estimation of human brain fluid clearance using intrathecal imaging contrast agents.Fluids and barriers of the CNS · 2026Observational
- Longitudinal CSF and Serum Biomarker Dynamics in Tofersen-TreatedInternational journal of molecular sciences · 2026Article
- Gene Targeted Therapies for Neurodegenerative Disorders: Strategies and Implications in ALS and SMA.Genes · 2026Review
- Antisense oligonucleotide-mediated knockdown therapy in two infants with severe KCNT1 epileptic encephalopathy.Nature medicine · 2026Article
- Long non-coding RNAs in neurodegenerative diseases - Molecular mechanisms, liquid biopsy biomarkers, and therapeutic targets: A review.Biomolecules & biomedicine · 2026Review
- In vivo self-assembled SOD1-siRNAs mitigate muscle atrophy and denervation in amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Article
- BLOC1S1 depletion via splice-switching oligonucleotides improves mitochondrial respiration and rescues ALS phenotypes.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Article
- Repeat-associated non-AUG translation as a common mechanism for the polyGln ataxias.Cell reports · 2026Article
- Development and pilot testing of U1 Adaptor therapy targeting SOD1 expression for dogs with degenerative myelopathy.Journal of veterinary internal medicine · 2026Article
- Oxidative Stress and Lysosomal Dysfunction in Neurodegenerative Diseases: Underlying Mechanisms and Nanotherapeutic Targeting Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Central Nervous System Biodistribution and Pharmacokinetics of Radiolabeled Tofersen in Rodents, Nonhuman Primates, and Humans.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- Non-cell autonomous autophagy in amyotrophic lateral sclerosis: A new promising target?Neurobiology of disease · 2026Review
109 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 4 institutions in 1 country.
Funding
Abstract
Mutations in superoxide dismutase 1 (SOD1) are responsible for 20% of familial ALS. Given the gain of toxic function in this dominantly inherited disease, lowering SOD1 mRNA and protein is predicted to provide therapeutic benefit. An early generation antisense oligonucleotide (ASO) targeting SOD1 was identified and tested in a phase I human clinical trial, based on modest protection in animal models of SOD1 ALS. Although the clinical trial provided encouraging safety data, the drug was not advanced because there was progress in designing other, more potent ASOs for CNS application. We have developed next-generation SOD1 ASOs that more potently reduce SOD1 mRNA and protein and extend survival by more than 50 days in SOD1G93A rats and by almost 40 days in SOD1G93A mice. We demonstrated that the initial loss of compound muscle action potential in SOD1G93A mice is reversed after a single dose of SOD1 ASO. Furthermore, increases in serum phospho-neurofilament heavy chain levels, a promising biomarker for ALS, are stopped by SOD1 ASO therapy. These results define a highly potent, new SOD1 ASO ready for human clinical trial and suggest that at least some components of muscle response can be reversed by therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.