ArticleJCI insight2016
Systemic restoration of UBA1 ameliorates disease in spinal muscular atrophy.
Article in JCI insight, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis 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.
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
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Systematic review and meta-analysis determining the benefits of in vivo genetic therapy in spinal muscular atrophy rodent models.Gene therapy · 2022Pooled it
- Comorbidities in spinal muscular atrophy and their impact on the course of the underlying disease: a real-life observational study.BMC musculoskeletal disorders · 2025Observational
- Transcriptional reprogramming in SMA mouse hearts reveals signatures of early heart failure and dysregulated calcium signaling.Human molecular genetics · 2025Article
- Treating neuromuscular diseases: unveiling gene therapy breakthroughs and pioneering future applications.Journal of biomedical science · 2025Review
- Patient-specific responses toMolecular therapy. Methods & clinical development · 2024Article
- Review
- Ubiquitination Insight from Spinal Muscular Atrophy-From Pathogenesis to Therapy: A Muscle Perspective.International journal of molecular sciences · 2024Review
- No significant sex differences in incidence or phenotype for the SMNΔ7 mouse model of spinal muscular atrophy.Neuromuscular disorders : NMD · 2024Article
- Modeling Spinal Muscular Atrophy in Zebrafish: Current Advances and Future Perspectives.International journal of molecular sciences · 2024Review
- Article
- Long-term muscle-specific overexpression of DOK7 in mice using AAV9-tMCK-DOK7.Molecular therapy. Nucleic acids · 2023Article
- Innovating spinal muscular atrophy models in the therapeutic era.Disease models & mechanisms · 2023Article
- Auranofin targets UBA1 and enhances UBA1 activity by facilitating ubiquitin trans-thioesterification to E2 ubiquitin-conjugating enzymes.Nature communications · 2023Article
- ALS-linked CCNF variant disrupts motor neuron ubiquitin homeostasis.Human molecular genetics · 2023Article
- WNT-β Catenin Signaling as a Potential Therapeutic Target for Neurodegenerative Diseases: Current Status and Future Perspective.Diseases (Basel, Switzerland) · 2023Review
- ABT1 modifies SMARD1 pathology via interactions with IGHMBP2 and stimulation of ATPase and helicase activity.JCI insight · 2023Article
- Sex Difference in Spinal Muscular Atrophy Patients - are Males More Vulnerable?Journal of neuromuscular diseases · 2023Article
- Autophagy in spinal muscular atrophy: from pathogenic mechanisms to therapeutic approaches.Frontiers in cellular neuroscience · 2023Review
- NSC Physiological Features in Spinal Muscular Atrophy: SMN Deficiency Effects on Neurogenesis.International journal of molecular sciences · 2022Review
- Mitochondrial Dysfunction in Spinal Muscular Atrophy.International journal of molecular sciences · 2022Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
The autosomal recessive neuromuscular disease spinal muscular atrophy (SMA) is caused by loss of survival motor neuron (SMN) protein. Molecular pathways that are disrupted downstream of SMN therefore represent potentially attractive therapeutic targets for SMA. Here, we demonstrate that therapeutic targeting of ubiquitin pathways disrupted as a consequence of SMN depletion, by increasing levels of one key ubiquitination enzyme (ubiquitin-like modifier activating enzyme 1 [UBA1]), represents a viable approach for treating SMA. Loss of UBA1 was a conserved response across mouse and zebrafish models of SMA as well as in patient induced pluripotent stem cell-derive motor neurons. Restoration of UBA1 was sufficient to rescue motor axon pathology and restore motor performance in SMA zebrafish. Adeno-associated virus serotype 9-UBA1 (AAV9-UBA1) gene therapy delivered systemic increases in UBA1 protein levels that were well tolerated over a prolonged period in healthy control mice. Systemic restoration of UBA1 in SMA mice ameliorated weight loss, increased survival and motor performance, and improved neuromuscular and organ pathology. AAV9-UBA1 therapy was also sufficient to reverse the widespread molecular perturbations in ubiquitin homeostasis that occur during SMA. We conclude that UBA1 represents a safe and effective therapeutic target for the treatment of both neuromuscular and systemic aspects of SMA.
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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.