ArticleHuman molecular genetics2016
Pharmacokinetics, pharmacodynamics, and efficacy of a small-molecule SMN2 splicing modifier in mouse models of spinal muscular atrophy.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Depleting prion protein using splice-switching small molecules.bioRxiv : the preprint server for biology · 2026Article
- Identification of p38 MAPK inhibition as a neuroprotective strategy for combinatorial SMA therapy.EMBO molecular medicine · 2025Article
- The effect of coadministration of D156844 and AR42 (REC-2282) on the survival and motor phenotype of mice with spinal muscular atrophy.Scientific reports · 2025Article
- Proprioceptive synaptic dysfunction is a key feature in mice and humans with spinal muscular atrophy.Brain : a journal of neurology · 2025Article
- Optimization of base editors for the functional correction of SMN2 as a treatment for spinal muscular atrophy.Nature biomedical engineering · 2024Article
- Chemistry, structure and function of approved oligonucleotide therapeutics.Nucleic acids research · 2023Review
- Autophagy regulation by RNA alternative splicing and implications in human diseases.Nature communications · 2022Review
- Dual SMN inducing therapies can rescue survival and motor unit function in symptomatic ∆7SMA mice.Neurobiology of disease · 2021Article
- Review
- Activation of Muscle-Specific Kinase (MuSK) Reduces Neuromuscular Defects in the Delta7 Mouse Model of Spinal Muscular Atrophy (SMA).International journal of molecular sciences · 2021Article
- Huntingtin-mediated axonal transport requires arginine methylation by PRMT6.Cell reports · 2021Article
- Minor snRNA gene delivery improves the loss of proprioceptive synapses on SMA motor neurons.JCI insight · 2020Article
- RNA-Targeted Therapies and High-Throughput Screening Methods.International journal of molecular sciences · 2020Review
- Gene specific therapies - the next therapeutic milestone in neurology.Neurological research and practice · 2020Review
- Specific inhibition of myostatin activation is beneficial in mouse models of SMA therapy.Human molecular genetics · 2019Article
- Risdiplam distributes and increases SMN protein in both the central nervous system and peripheral organs.Pharmacology research & perspectives · 2018Article
- Treating pediatric neuromuscular disorders: The future is now.American journal of medical genetics. Part A · 2018Review
- Inherited Retinal Disease Therapies Targeting Precursor Messenger Ribonucleic Acid.Vision (Basel, Switzerland) · 2017Review
- RNA-sequencing of a mouse-model of spinal muscular atrophy reveals tissue-wide changes in splicing of U12-dependent introns.Nucleic acids research · 2017Article
- Advances in modeling and treating spinal muscular atrophy.Current opinion in neurology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 4 institutions in 2 countries.
Funding
Abstract
Spinal muscular atrophy (SMA) is caused by the loss or mutation of both copies of the survival motor neuron 1 (SMN1) gene. The related SMN2 gene is retained, but due to alternative splicing of exon 7, produces insufficient levels of the SMN protein. Here, we systematically characterize the pharmacokinetic and pharmacodynamics properties of the SMN splicing modifier SMN-C1. SMN-C1 is a low-molecular weight compound that promotes the inclusion of exon 7 and increases production of SMN protein in human cells and in two transgenic mouse models of SMA. Furthermore, increases in SMN protein levels in peripheral blood mononuclear cells and skin correlate with those in the central nervous system (CNS), indicating that a change of these levels in blood or skin can be used as a non-invasive surrogate to monitor increases of SMN protein levels in the CNS. Consistent with restored SMN function, SMN-C1 treatment increases the levels of spliceosomal and U7 small-nuclear RNAs and corrects RNA processing defects induced by SMN deficiency in the spinal cord of SMNΔ7 SMA mice. A 100% or greater increase in SMN protein in the CNS of SMNΔ7 SMA mice robustly improves the phenotype. Importantly, a ∼50% increase in SMN leads to long-term survival, but the SMA phenotype is only partially corrected, indicating that certain SMA disease manifestations may respond to treatment at lower doses. Overall, we provide important insights for the translation of pre-clinical data to the clinic and further therapeutic development of this series of molecules for SMA treatment.
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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.