ArticlePloS one2014
Systems biology investigation of cAMP modulation to increase SMN levels for the treatment of spinal muscular atrophy.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.
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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
10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 17 citations in OpenAlex.
- Salbutamol in 5q spinal muscular atrophy: a systematic review and meta-analysis of efficacy and safety.European journal of pediatrics · 2025Pooled it
- Drug treatment for spinal muscular atrophy types II and III.The Cochrane database of systematic reviews · 2020Pooled it
- Adenylyl Cyclases as Therapeutic Targets in Neuroregeneration.International journal of molecular sciences · 2025Review
- A transcriptomics-based drug repositioning approach to identify drugs with similar activities for the treatment of muscle pathologies in spinal muscular atrophy (SMA) models.Human molecular genetics · 2024Article
- Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy.Scientific reports · 2023Article
- Drug Discovery of Spinal Muscular Atrophy (SMA) from the Computational Perspective: A Comprehensive Review.International journal of molecular sciences · 2021Review
- Using Systems Biology and Mathematical Modeling Approaches in the Discovery of Therapeutic Targets for Spinal Muscular Atrophy.Advances in neurobiology · 2018Review
- Hyperlipidemia-induced cholesterol crystal production by endothelial cells promotes atherogenesis.Nature communications · 2017Article
- The effects of C5-substituted 2,4-diaminoquinazolines on selected transcript expression in spinal muscular atrophy cells.PloS one · 2017Article
- Salbutamol inhibits ubiquitin-mediated survival motor neuron protein degradation in spinal muscular atrophy cells.Biochemistry and biophysics reports · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Spinal muscular atrophy (SMA), a leading genetic cause of infant death worldwide, is an autosomal recessive disorder caused by the loss of SMN1 (survival motor neuron 1), which encodes the protein SMN. The loss of SMN1 causes a deficiency in SMN protein levels leading to motor neuron cell death in the anterior horn of the spinal cord. SMN2, however, can also produce some functional SMN to partially compensate for loss of SMN1 in SMA suggesting increasing transcription of SMN2 as a potential therapy to treat patients with SMA. A cAMP response element was identified on the SMN2 promoter, implicating cAMP activation as a step in the transcription of SMN2. Therefore, we investigated the effects of modulating the cAMP signaling cascade on SMN production in vitro and in silico. SMA patient fibroblasts were treated with the cAMP signaling modulators rolipram, salbutamol, dbcAMP, epinephrine and forskolin. All of the modulators tested were able to increase gem formation, a marker for SMN protein in the nucleus, in a dose-dependent manner. We then derived two possible mathematical models simulating the regulation of SMN2 expression by cAMP signaling. Both models fit well with our experimental data. In silico treatment of SMA fibroblasts simultaneously with two different cAMP modulators resulted in an additive increase in gem formation. This study shows how a systems biology approach can be used to develop potential therapeutic targets for treating SMA.
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Registered trials
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