ArticleScientific reports2015
Spinal muscular atrophy phenotype is ameliorated in human motor neurons by SMN increase via different novel RNA therapeutic approaches.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- RNA biomarkers in spinal muscular atrophy: enhancing pathogenesis understanding and guiding precision medicine.Cellular and molecular life sciences : CMLS · 2026Review
- AAV2-mediated intravitreal delivery of exon-specific U1 snRNA rescues optic neuropathy in familial dysautonomia.Molecular therapy. Nucleic acids · 2026Article
- Patient-specific responses toMolecular therapy. Methods & clinical development · 2024Article
- Antisense Oligonucleotides (ASOs) in Motor Neuron Diseases: A Road to Cure in Light and Shade.International journal of molecular sciences · 2024Review
- Antisense Oligonucleotide Therapy for the Nervous System: From Bench to Bedside with Emphasis on Pediatric Neurology.Pharmaceutics · 2022Review
- Rescue of a familial dysautonomia mouse model by AAV9-Exon-specific U1 snRNA.American journal of human genetics · 2022Article
- Cerebral Organoids and Antisense Oligonucleotide Therapeutics: Challenges and Opportunities.Frontiers in molecular neuroscience · 2022Review
- An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients.iScience · 2021Article
- The Importance of Digging into the Genetics ofInternational journal of molecular sciences · 2021Review
- Impairment of the neurotrophic signaling hub B-Raf contributes to motoneuron degeneration in spinal muscular atrophy.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Patient-derived iPSC modeling of rare neurodevelopmental disorders: Molecular pathophysiology and prospective therapies.Neuroscience and biobehavioral reviews · 2021Review
- Genome Editing in iPSC-Based Neural Systems: From Disease Models to Future Therapeutic Strategies.Frontiers in genome editing · 2021Review
- The Potential of Induced Pluripotent Stem Cells to Test Gene Therapy Approaches for Neuromuscular and Motor Neuron Disorders.Frontiers in cell and developmental biology · 2021Review
- Synaptotagmin 13 is neuroprotective across motor neuron diseases.Acta neuropathologica · 2020Article
- Spinal Muscular Atrophy Modeling and Treatment Advances by Induced Pluripotent Stem Cells Studies.Stem cell reviews and reports · 2019Review
- Rescue of spinal muscular atrophy mouse models with AAV9-Exon-specific U1 snRNA.Nucleic acids research · 2019Article
- Molecular Mechanisms and Determinants of Innovative Correction Approaches in Coagulation Factor Deficiencies.International journal of molecular sciences · 2019Review
- Key role of SMN/SYNCRIP and RNA-Motif 7 in spinal muscular atrophy: RNA-Seq and motif analysis of human motor neurons.Brain : a journal of neurology · 2019Article
- Organs to Cells and Cells to Organoids: The Evolution ofFrontiers in cellular neuroscience · 2019Review
- RNA Splicing and Disease: Animal Models to Therapies.Trends in genetics : TIG · 2019Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinal muscular atrophy (SMA) is a primary genetic cause of infant mortality due to mutations in the Survival Motor Neuron (SMN) 1 gene. No cure is available. Antisense oligonucleotides (ASOs) aimed at increasing SMN levels from the paralogous SMN2 gene represent a possible therapeutic strategy. Here, we tested in SMA human induced pluripotent stem cells (iPSCs) and iPSC-differentiated motor neurons, three different RNA approaches based on morpholino antisense targeting of the ISSN-1, exon-specific U1 small nuclear RNA (ExSpeU1), and Transcription Activator-Like Effector-Transcription Factor (TALE-TF). All strategies act modulating SMN2 RNA: ASO affects exon 7 splicing, TALE-TF increase SMN2 RNA acting on the promoter, while ExSpeU1 improves pre-mRNA processing. These approaches induced up-regulation of full-length SMN mRNA and differentially affected the Delta-7 isoform: ASO reduced this isoform, while ExSpeU1 and TALE-TF increased it. All approaches upregulate the SMN protein and significantly improve the in vitro SMA motor neurons survival. Thus, these findings demonstrate that therapeutic tools that act on SMN2 RNA are able to rescue the SMA disease phenotype. Our data confirm the feasibility of SMA iPSCs as in vitro disease models and we propose novel RNA approaches as potential therapeutic strategies for treating SMA and other genetic neurological disorders.
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