ArticleJCI insight2019
Brain pharmacology of intrathecal antisense oligonucleotides revealed through multimodal imaging.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 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
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Who cites it
71 citing papers in PubMed, 101 citations in OpenAlex.
- LRRK2-targeting antisense oligonucleotide in Parkinson's disease: a phase 1 randomized controlled trial.Nature medicine · 2026Trial
- Albumin-binding dendrimer-conjugated siRNA enables safe and effective gene silencing throughout the central nervous system.Nucleic acids research · 2026Article
- Safety and toxicity assessment of antisense oligonucleotides in brain-relevant human cellular models.Molecular therapy. Nucleic acids · 2026Review
- Single-dose administration of therapeutic divalent siRNA targeting MECP2 prevents lethality in an MECP2 duplication mouse model.Nature communications · 2026Article
- Antibody-oligonucleotide conjugates: an emerging modality for precision RNA therapeutics.Antibody therapeutics · 2026Review
- The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026Review
- Estimation of human brain fluid clearance using intrathecal imaging contrast agents.Fluids and barriers of the CNS · 2026Observational
- From classic circuits to novel mechanisms: How lncRNA, neuroinflammation, and iPSC models address the translational crisis in PTSD research.Comprehensive psychoneuroendocrinology · 2026Review
- Mechanistic multiphysics modeling reveals how blood pulsation drives CSF flow, pressure, and brain deformation under physiological and injection conditions.Fluids and barriers of the CNS · 2026Article
- Beyond muscle: Delivering RNA therapeutics to the CNS in Duchenne muscular dystrophy.Journal of neuromuscular diseases · 2026Review
- Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system.Advanced drug delivery reviews · 2026Review
- Acute neuronal inhibition response caused by phosphorothioate antisense oligonucleotides following local delivery to the central nervous system.Nucleic acids research · 2026Article
- Transient acute neuronal activation response caused by high concentrations of oligonucleotides in the cerebral spinal fluid.Nucleic acids research · 2026Article
- The Expanding Role of Non-Coding RNAs in Neurodegenerative Diseases: From Biomarkers to Therapeutic Targets.Pharmaceuticals (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
- Comparison ofMolecular therapy. Nucleic acids · 2025Article
- AAV delivery of artificial miRNA targeting MAPT for the reduction of tau pathology in Alzheimer's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Early-life gut microbiome maturity regulates blood-brain barrier and cognitive development.Gut microbes · 2025Article
- Mass Spectrometry Imaging Reveals the Distribution of a GABRG2 Targeting Antisense Oligonucleotide and Its Functional Effect in Rat Brain.ACS chemical neuroscience · 2025Article
11 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
24 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intrathecal (IT) delivery and pharmacology of antisense oligonucleotides (ASOs) for the CNS have been successfully developed to treat spinal muscular atrophy. However, ASO pharmacokinetic (PK) and pharmacodynamic (PD) properties remain poorly understood in the IT compartment. We applied multimodal imaging techniques to elucidate the IT PK and PD of unlabeled, radioactively labeled, or fluorescently labeled ASOs targeting ubiquitously expressed or neuron-specific RNAs. Following lumbar IT bolus injection in rats, all ASOs spread rostrally along the neuraxis, adhered to meninges, and were partially cleared to peripheral lymph nodes and kidneys. Rapid association with the pia and arterial walls preceded passage of ASOs across the glia limitans, along arterial intramural basement membranes, and along white-matter axonal bundles. Several neuronal and glial cell types accumulated ASOs over time, with evidence of probable glial accumulation preceding neuronal uptake. IT doses of anti-GluR1 and anti-Gabra1 ASOs markedly reduced the mRNA and protein levels of their respective neurotransmitter receptor protein targets by 2 weeks and anti-Gabra1 ASOs also reduced binding of the GABAA receptor PET ligand 18F-flumazenil in the brain over 4 weeks. Our multimodal imaging approaches elucidate multiple transport routes underlying the CNS distribution, clearance, and efficacy of IT-dosed ASOs.
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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.