ArticleNucleic acids research2023
Diverse targets of SMN2-directed splicing-modulating small molecule therapeutics for spinal muscular atrophy.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
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
35 citing papers in PubMed, 39 citations in OpenAlex.
- Oral splicing modulator branaplam in Huntington's disease: a phase 2 randomized controlled trial.Nature medicine · 2026Trial
- Nusinersen: the antisense oligonucleotide at the forefront of spinal muscular atrophy treatment.RNA biology · 2026Review
- Real-world 12-month outcomes of Risdiplam in spinal muscular atrophy types 2 and 3: A Brazilian cohort.Clinics (Sao Paulo, Brazil) · 2026Article
- A p53-ΔNp73 signaling axis drives selective motor neuron degeneration in spinal muscular atrophy.bioRxiv : the preprint server for biology · 2026Article
- Longitudinal Transcriptomic Analysis Reveals Systemic Effects of Risdiplam in Adults with Spinal Muscular Atrophy.Brain sciences · 2026Article
- Tunable gene control via RNA splicing with a clinically approved small molecule.Nature communications · 2026Article
- SpliceHarmonization: an integrated method for identifying RNA splicing events in therapeutics for splicing modulation.Bioinformatics (Oxford, England) · 2026Article
- Gene Targeted Therapies for Neurodegenerative Disorders: Strategies and Implications in ALS and SMA.Genes · 2026Review
- Modified Polycyclic Compounds Rescue Mis-splicing in Myotonic Dystrophy Type 1 Disease Models.ACS chemical biology · 2026Article
- The survival motor neuron protein: structure, functions, stability, and therapeutic targeting.Frontiers in cellular neuroscience · 2026Review
- Survival motor neuron protein-independent amelioration of spinal muscular atrophy by pharmacological inhibition of c-Jun-NHBrain communications · 2026Article
- A therapeutic antisense oligonucleotide encompassing 2'-NAR molecular medicine · 2026Article
- Spinal muscular atrophy in the disease-modifying therapy era: successes, limitations and future directions.Frontiers in molecular medicine · 2026Review
- Article
- Alternative Splicing: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Systematic characterization of existing and novel inducible transgenic systems in human pluripotent stem cells after prolonged differentiation.bioRxiv : the preprint server for biology · 2025Article
- A Chemically Induced CRISPR/dCas13Journal of medicinal chemistry · 2025Article
- A portable poison exon for small-molecule control of mammalian gene expression.Nature methods · 2025Article
- Epigenetic regulation in spinal muscular atrophy: emerging areas and future directions.Orphanet journal of rare diseases · 2025Review
- Significance of gene therapy in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Designing an RNA-interacting molecule that displays high therapeutic efficacy while retaining specificity within a broad concentration range remains a challenging task. Risdiplam is an FDA-approved small molecule for the treatment of spinal muscular atrophy (SMA), the leading genetic cause of infant mortality. Branaplam is another small molecule which has undergone clinical trials. The therapeutic merit of both compounds is based on their ability to restore body-wide inclusion of Survival Motor Neuron 2 (SMN2) exon 7 upon oral administration. Here we compare the transcriptome-wide off-target effects of these compounds in SMA patient cells. We captured concentration-dependent compound-specific changes, including aberrant expression of genes associated with DNA replication, cell cycle, RNA metabolism, cell signaling and metabolic pathways. Both compounds triggered massive perturbations of splicing events, inducing off-target exon inclusion, exon skipping, intron retention, intron removal and alternative splice site usage. Our results of minigenes expressed in HeLa cells provide mechanistic insights into how these molecules targeted towards a single gene produce different off-target effects. We show the advantages of combined treatments with low doses of risdiplam and branaplam. Our findings are instructive for devising better dosing regimens as well as for developing the next generation of small molecule therapeutics aimed at splicing modulation.
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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.