ArticleEuropean journal of human genetics : EJHG2013
Severe SMA mice show organ impairment that cannot be rescued by therapy with the HDACi JNJ-26481585.
Article in European journal of human genetics : EJHG, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 3 of them syntheses 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.
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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
48 citing papers in PubMed, 3 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- Drug treatment for spinal muscular atrophy types II and III.The Cochrane database of systematic reviews · 2020Pooled it
- Drug treatment for spinal muscular atrophy type I.The Cochrane database of systematic reviews · 2019Pooled it
- Cardiac pathology in spinal muscular atrophy: a systematic review.Orphanet journal of rare diseases · 2017Pooled it
- Long-term comparative analysis of AAV9-mediated gene replacement therapies for spinal muscular atrophy in mice.Nature communications · 2026Article
- Spinal muscular atrophy: Biology, pathogenesis, and therapeutic advances.Therapeutic advances in neurological disorders · 2026Review
- Survival motor neuron protein-independent amelioration of spinal muscular atrophy by pharmacological inhibition of c-Jun-NHBrain communications · 2026Article
- Alterations in cardiac function correlate with a disruption in fatty acid metabolism in a mouse model of SMA.Human molecular genetics · 2025Article
- Improved gene therapy for spinal muscular atrophy in mice using codon-optimized hSMN1 transgene and hSMN1 gene-derived promotor.EMBO molecular medicine · 2024Article
- What could be the function of the spinal muscular atrophy-causing protein SMN in macrophages?Frontiers in immunology · 2024Review
- Biomarkers in 5q-associated spinal muscular atrophy-a narrative review.Journal of neurology · 2023Review
- Innovating spinal muscular atrophy models in the therapeutic era.Disease models & mechanisms · 2023Article
- Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy.Scientific reports · 2023Article
- Article
- Evaluating Efficacy of Peptide-Delivered Oligonucleotides Using the Severe Taiwanese SMA Mouse Model.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models.iScience · 2021Article
- Metabolic Dysfunction in Spinal Muscular Atrophy.International journal of molecular sciences · 2021Review
- Spinal muscular atrophy: Broad disease spectrum and sex-specific phenotypes.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy.Brain sciences · 2021Review
- Review
- A survey of transcripts generated by spinal muscular atrophy genes.Biochimica et biophysica acta. Gene regulatory mechanisms · 2020Review
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 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinal muscular atrophy (SMA) is the leading genetic cause of early childhood death worldwide and no therapy is available today. Many drugs, especially histone deacetylase inhibitors (HDACi), increase SMN levels. As all HDACi tested so far only mildly ameliorate the SMA phenotype or are unsuitable for use in humans, there is still need to identify more potent drugs. Here, we assessed the therapeutic power of the pan-HDACi JNJ-26481585 for SMA, which is currently used in various clinical cancer trials. When administered for 64 h at 100 nM, JNJ-26481585 upregulated SMN levels in SMA fibroblast cell lines, including those from non-responders to valproic acid. Oral treatment of Taiwanese SMA mice and control littermates starting at P0 showed no overt extension of lifespan, despite mild improvements in motor abilities and weight progression. Many treated and untreated animals showed a very rapid decline or unexpected sudden death. We performed exploratory autopsy and histological assessment at different disease stages and found consistent abnormalities in the intestine, heart and lung and skeletal muscle vasculature of SMA animals, which were not prevented by JNJ-26481585 treatment. Interestingly, some of these features may be only indirectly caused by α-motoneuron function loss but may be major life-limiting factors in the course of disease. A better understanding of - primary or secondary - non-neuromuscular organ involvement in SMA patients may improve standard of care and may lead to reassessment of how to investigate SMA patients clinically.
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Registered trials
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