ArticleJCI insight2021
α-Synuclein antisense oligonucleotides as a disease-modifying therapy for Parkinson's disease.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
81 citing papers in PubMed, 2 syntheses or guidelines pooled it, 127 citations in OpenAlex.
- Are Therapies That Target α-Synuclein Effective at Halting Parkinson's Disease Progression? A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Molecular Pathways Involved in LRRK2-Linked Parkinson's Disease: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Does genetic testing remain relevant in advanced Parkinson's disease?Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Neural Stem Cell-Derived Extracellular Vesicles Improve CNS Delivery and Therapeutic Efficacy of Antisense Oligonucleotide in Amyotrophic Lateral Sclerosis.Journal of extracellular vesicles · 2026Article
- The irony of Parkinson's disease: Converging mechanisms of redox imbalance and ferroptosis.Redox biology · 2026Review
- Gut-brain axis dysregulation in Parkinson's disease: Mechanisms linking microbiota to neuroinflammation and α-synuclein pathology.Journal of pharmaceutical analysis · 2026Review
- Gaps in the Parkinson's disease therapeutic clinical pipeline: A focus on approaches targeting disease pathobiology.Journal of Parkinson's disease · 2026Review
- Role of aging‑related cytokines in neurodegenerative disease (Review).International journal of molecular medicine · 2026Review
- Overcoming Oxidative Stress in Parkinson's Disease: NADPH Oxidase 4 (NOX4) as a Potential Therapeutic Target.Antioxidants (Basel, Switzerland) · 2026Review
- Antisense Oligonucleotide Therapeutics Targeting Age-Related Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Review
- Identification of KHS-101 as a Transcription Factor EB Activator to Promote α-Synuclein Degradation.International journal of molecular sciences · 2026Article
- Research progress on the α-synuclein-lysosome axis in Parkinson's disease: molecular mechanisms of protein aggregation, autophagy dysfunction, and therapeutic targeting.Frontiers in neuroscience · 2026Review
- Nucleic acid therapeutics in neurodegenerative disorders: emerging technologies and clinical landscape.Molecular neurodegeneration advances · 2026Review
- One organelle to rule them all: enhancement of lysosomal activity as a therapeutic modality for protein misfolding neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- Targeting Non-coding RNAs in Neurodegeneration: Advances in Therapeutic RNA Modalities and Next-Gen Delivery Technologies.Current Alzheimer research · 2026Review
- Prions and protein aggregates as pathogens, self-propagating structures, biomarkers, and therapeutic targets.Microbiology and molecular biology reviews : MMBR · 2025Review
- Targeted α-Synuclein mRNA Degradation by PMO-Based RNA-Degrading Chimeras.bioRxiv : the preprint server for biology · 2025Article
- A manifesto for Alzheimer's disease drug discovery in the era of disease-modifying therapies.Molecular neurodegeneration · 2025Review
- Recent advances in targeting LRRK2 for Parkinson's disease treatment.Journal of translational medicine · 2025Review
21 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
25 authors at 4 institutions in 1 country.
Funding
Abstract
Parkinson's disease (PD) is a prevalent neurodegenerative disease with no approved disease-modifying therapies. Multiplications, mutations, and single nucleotide polymorphisms in the SNCA gene, encoding α-synuclein (aSyn) protein, either cause or increase risk for PD. Intracellular accumulations of aSyn are pathological hallmarks of PD. Taken together, reduction of aSyn production may provide a disease-modifying therapy for PD. We show that antisense oligonucleotides (ASOs) reduce production of aSyn in rodent preformed fibril (PFF) models of PD. Reduced aSyn production leads to prevention and removal of established aSyn pathology and prevents dopaminergic cell dysfunction. In addition, we address the translational potential of the approach through characterization of human SNCA-targeting ASOs that efficiently suppress the human SNCA transcript in vivo. We demonstrate broad activity and distribution of the human SNCA ASOs throughout the nonhuman primate brain and a corresponding decrease in aSyn cerebral spinal fluid (CSF) levels. Taken together, these data suggest that, by inhibiting production of aSyn, it may be possible to reverse established pathology; thus, these data support the development of SNCA ASOs as a potential disease-modifying therapy for PD and related synucleinopathies.
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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.