ArticleThe Journal of pharmacology and experimental therapeutics2014
Pharmacology of a central nervous system delivered 2'-O-methoxyethyl-modified survival of motor neuron splicing oligonucleotide in mice and nonhuman primates.
Article in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 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.
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Who cites it
164 citing papers in PubMed, 2 syntheses or guidelines pooled it, 269 citations in OpenAlex.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- Guidance for the care of neuromuscular patients during the COVID-19 pandemic outbreak from the French Rare Health Care for Neuromuscular Diseases Network.Revue neurologique · 2020Guideline
- Safety and toxicity assessment of antisense oligonucleotides in brain-relevant human cellular models.Molecular therapy. Nucleic acids · 2026Review
- Review
- Phenotypic screening for small molecules that lower PrP in cultured cells.Molecular and cellular neurosciences · 2026Article
- Disease-Modifying Therapies in Spinal Muscular Atrophy: Neurodevelopmental and Behavioral Outcomes in the Treatment Era.Advances in therapy · 2026Review
- The Hallmarks of Glioblastoma: Functional Interplay Between Long Non-Coding RNAs and RNA-Binding Proteins.Cells · 2026Review
- Enhanced splicing modulation by NMA-modified antisense oligonucleotides.Nucleic acids research · 2026Article
- Phenotypic screening for small molecules that lower PrP in cultured cells.bioRxiv : the preprint server for biology · 2026Article
- A historical perspective on the development of antisense oligonucleotide treatments for Duchenne muscular dystrophy and spinal muscular atrophy.Journal of neuromuscular diseases · 2026Review
- Beyond muscle: Delivering RNA therapeutics to the CNS in Duchenne muscular dystrophy.Journal of neuromuscular diseases · 2026Review
- Real-world evidence on nusinersen treatment of persons with SMA: a focused review.Journal of neuromuscular diseases · 2026Review
- Transient acute neuronal activation response caused by high concentrations of oligonucleotides in the cerebral spinal fluid.Nucleic acids research · 2026Article
- RNA-based therapeutic opportunities for the treatment of kidney diseases.Nature reviews. Nephrology · 2026Review
- Genetic medicines for epilepsy: unlocking new avenues for seizure control.Frontiers in bioengineering and biotechnology · 2026Review
- Review
- Pharmacokinetics of therapies approved for spinal muscular atrophy: A narrative review of current evidence.The Journal of international medical research · 2025Review
- Therapeutic antisense oligonucleotide mitigates retinal dysfunction in a pig model of CLN3 Batten disease.Nucleic acids research · 2025Article
- Correcting tau isoform ratios with a long-acting antisense oligonucleotide alleviates 4R-tauopathy phenotypes.Molecular therapy. Nucleic acids · 2025Article
- Intra-amniotic antisense oligonucleotide treatment improves phenotypes in preclinical models of spinal muscular atrophy.Science translational medicine · 2025Article
104 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
13 authors at 2 institutions in 1 country.
Funding
Abstract
Spinal muscular atrophy (SMA) is a debilitating neuromuscular disease caused by the loss of survival of motor neuron (SMN) protein. Previously, we demonstrated that ISIS 396443, an antisense oligonucleotide (ASO) targeted to the SMN2 pre-mRNA, is a potent inducer of SMN2 exon 7 inclusion and SMN protein expression, and improves function and survival of mild and severe SMA mouse models. Here, we demonstrate that ISIS 396443 is the most potent ASO in central nervous system (CNS) tissues of adult mice, compared with several other chemically modified ASOs. We evaluated methods of ISIS 396443 delivery to the CNS and characterized its pharmacokinetics and pharmacodynamics in rodents and nonhuman primates (NHPs). Intracerebroventricular bolus injection is a more efficient method of delivering ISIS 396443 to the CNS of rodents, compared with i.c.v. infusion. For both methods of delivery, the duration of ISIS 396443-mediated SMN2 splicing correction is long lasting, with maximal effects still observed 6 months after treatment discontinuation. Administration of ISIS 396443 to the CNS of NHPs by a single intrathecal bolus injection results in widespread distribution throughout the spinal cord. Based upon these preclinical studies, we have advanced ISIS 396443 into clinical development.
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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.