ArticleNature medicine2022
Antisense oligonucleotide silencing of FUS expression as a therapeutic approach in amyotrophic lateral sclerosis.
Article in Nature medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 1 of them a synthesis that pooled it.
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Who cites it
149 citing papers in PubMed, 1 synthesis or guideline pooled it, 253 citations in OpenAlex.
- Ultra-Orphan drug development for GNE Myopathy: A synthetic literature review and meta-analysis.Journal of neuromuscular diseases · 2025Pooled it
- Therapeutic frontiers in ALS: iPSC-based drug discovery, cell therapy, and gene therapy-Advances through 2026.Regenerative therapy · 2026Review
- FUS controls muscle differentiation through phase separation-mediated recruitment of the transcription factors MEF2 and ETV5.The EMBO journal · 2026Article
- Review
- G-Quadruplexes: Structural Diversity and Emerging Roles in Biomolecular Condensation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Preparing Amyotrophic Lateral Sclerosis Clinics to Provide Longitudinal Care for Individuals Carrying ALS Risk Variants.Neurology. Genetics · 2026Article
- Intravenous administration of an engineered AAV9-gene-silencing vector suppresses human SOD1 and extends survival in an ALS mouse model.Nature communications · 2026Article
- FUS-associated ALS in Taiwan: genetic spectrum, clinical features, and a founder haplotype of p.H517D.Journal of neurology · 2026Article
- Comprehensive clinical and genetic architecture of familial amyotrophic lateral sclerosis in China: A 15-year cohort study with 302 families.Neural regeneration research · 2026Article
- Paying for precision: funding approaches for N-of-1 trials of individualized gene targeted therapies.Orphanet journal of rare diseases · 2026Review
- BDNF insufficiency exacerbates ALS progression.Cell reports. Medicine · 2026Article
- RNArchitects: how hnRNPs shape neuronal landscapes.Brain : a journal of neurology · 2026Review
- RNA targeting therapy for a prenatally enriched potassium channel associated with severe childhood epilepsy and premature death.Nature communications · 2026Article
- Machine Learning-Guided Engineering of Protein Phase Separation Properties in Immune Regulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 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
- Large-scale exome analyses reveal new rare variant contributions in amyotrophic lateral sclerosis.Nature genetics · 2026Article
- Chemical and Molecular Strategies in Restoring Autophagic Flux in TDP-43 Proteinopathy.Molecules (Basel, Switzerland) · 2026Review
- Granules Gone Rogue: Nuclear and Cytoplasmic Ribonucleoprotein Structures in Amyotrophic Lateral Sclerosis-Fused in Sarcoma (ALS-FUS) Pathology.Molecular neurobiology · 2026Review
- Article
89 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Fused in sarcoma (FUS) is an RNA-binding protein that is genetically and pathologically associated with rare and aggressive forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). To explore the mechanisms by which mutant FUS causes neurodegeneration in ALS-FTD, we generated a series of FUS knock-in mouse lines that express the equivalent of ALS-associated mutant FUSP525L and FUSΔEX14 protein. In FUS mutant mice, we show progressive, age-dependent motor neuron loss as a consequence of a dose-dependent gain of toxic function, associated with the insolubility of FUS and related RNA-binding proteins. In this disease-relevant mouse model of ALS-FUS, we show that ION363, a non-allele-specific FUS antisense oligonucleotide, efficiently silences Fus and reduces postnatal levels of FUS protein in the brain and spinal cord, delaying motor neuron degeneration. In a patient with ALS with a FUSP525L mutation, we provide preliminary evidence that repeated intrathecal infusions of ION363 lower wild-type and mutant FUS levels in the central nervous system, resulting in a marked reduction in the burden of FUS aggregates that are a pathological hallmark of disease. In mouse genetic and human clinical studies, we provide evidence in support of FUS silencing as a therapeutic strategy in FUS-dependent ALS and FTD.
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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.