ArticleMolecular therapy. Nucleic acids2017
LRRK2 Antisense Oligonucleotides Ameliorate α-Synuclein Inclusion Formation in a Parkinson's Disease Mouse Model.
Article in Molecular therapy. Nucleic acids, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 131 papers, 1 of them a synthesis that pooled it.
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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
131 citing papers in PubMed, 1 synthesis or guideline pooled it, 211 citations in OpenAlex.
- Molecular Pathways Involved in LRRK2-Linked Parkinson's Disease: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- LRRK2-targeting antisense oligonucleotide in Parkinson's disease: a phase 1 randomized controlled trial.Nature medicine · 2026Trial
- Leucine-rich repeat kinase 2 (LRRK2): balancing cellular homeostasis and Parkinson's disease (PD) pathogenesis.Annals of medicine · 2026Review
- Glioma-induced DNMT3A reduction in microglia promotes an anti-tumoral phenotype.Cell death and differentiation · 2026Article
- Chemical Genetic Targeting of the LRRK2 GTPase Domain.bioRxiv : the preprint server for biology · 2026Article
- Gaps in the Parkinson's disease therapeutic clinical pipeline: A focus on approaches targeting disease pathobiology.Journal of Parkinson's disease · 2026Review
- Multi-cohort, cross-species urinary proteomics reveals signatures of LRRK2 dysfunction in Parkinson's disease.Molecular systems biology · 2026Article
- Pathological Protein Targets in Parkinson's Disease: Progress Towards the Development of Disease-Modifying Therapies.CNS drugs · 2026Review
- Role of LRRK2 in physiological activities, diseases, and therapy.Chinese medical journal · 2026Review
- Beyond muscle: Delivering RNA therapeutics to the CNS in Duchenne muscular dystrophy.Journal of neuromuscular diseases · 2026Review
- Nucleic acid therapeutics in neurodegenerative disorders: emerging technologies and clinical landscape.Molecular neurodegeneration advances · 2026Review
- LRRK2 mediates haloperidol-induced changes in indirect pathway striatal projection neurons.Molecular psychiatry · 2025Article
- Biomarkers and therapeutic strategies targeting microglia in neurodegenerative diseases: current status and future directions.Molecular neurodegeneration · 2025Review
- RNA Therapeutics: Focus on Antisense Oligonucleotides in the Nervous System.Biomolecules & therapeutics · 2025Review
- Leucine-rich repeat kinase 2 biomarkers for Parkinson's disease.The Biochemical journal · 2025Review
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- Genetic mutations in kinases: a comprehensive review on marketed inhibitors and unexplored targets in Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- The design and development of LRRK2 inhibitors as novel therapeutics for Parkinson's disease.Future medicinal chemistry · 2025Review
- Significance of gene therapy in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- Quantifying and mitigating motor phenotypes induced by antisense oligonucleotides in the central nervous system.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
71 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
No treatments exist to slow or halt Parkinson's disease (PD) progression; however, inhibition of leucine-rich repeat kinase 2 (LRRK2) activity represents one of the most promising therapeutic strategies. Genetic ablation and pharmacological LRRK2 inhibition have demonstrated promise in blocking α-synuclein (α-syn) pathology. However, LRRK2 kinase inhibitors may reduce LRRK2 activity in several tissues and induce systemic phenotypes in the kidney and lung that are undesirable. Here, we test whether antisense oligonucleotides (ASOs) provide an alternative therapeutic strategy, as they can be restricted to the CNS and provide a stable, long-lasting reduction of protein throughout the brain. Administration of LRRK2 ASOs to the brain reduces LRRK2 protein levels and fibril-induced α-syn inclusions. Mice exposed to α-syn fibrils treated with LRRK2 ASOs show more tyrosine hydroxylase (TH)-positive neurons compared to control mice. Furthermore, intracerebral injection of LRRK2 ASOs avoids unwanted phenotypes associated with loss of LRRK2 expression in the periphery. This study further demonstrates that a reduction of endogenous levels of normal LRRK2 reduces the formation of α-syn inclusions. Importantly, this study points toward LRRK2 ASOs as a potential therapeutic strategy for preventing PD-associated pathology and phenotypes without causing potential adverse side effects in peripheral tissues associated with LRRK2 inhibition.
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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.