ArticleThe Journal of clinical investigation2020
Muscle-specific SMN reduction reveals motor neuron-independent disease in spinal muscular atrophy models.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 98 citations in OpenAlex.
- Targeted knockdown of Smn in muscle stem cells induces non-cell autonomous loss of motor neurons.Brain : a journal of neurology · 2026Article
- Survival Motor Neuron Protein Requirement-Supply Mismatch in Spinal Muscular Atrophy: A Conceptual Framework.Advances in therapy · 2026Review
- Temperature-induced symptoms in adolescents and adults with spinal muscular atrophy.Journal of neuromuscular diseases · 2026Article
- Haloperidol induces neuroprotection and enhances neuromuscular function in both murine and human models of spinal muscular atrophy.Experimental & molecular medicine · 2026Article
- Fibro-adipogenic progenitor cells from murine SMA muscles are intrinsically adipogenic.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Therapeutic strategies for spinal muscular atrophy: the history and future perspective.Frontiers in human neuroscience · 2026Review
- Spinal muscular atrophy: Biology, pathogenesis, and therapeutic advances.Therapeutic advances in neurological disorders · 2026Review
- Cerebellar defects are a primary pathology in mouse models of spinal muscular atrophy.Brain pathology (Zurich, Switzerland) · 2025Article
- Drug Candidate BIO101 for Spinal Muscular Atrophy as Monotherapy or Combined With the Antisense Oligonucleotide ASO-10-27.Journal of cachexia, sarcopenia and muscle · 2025Article
- Padua Days on Muscle and Mobility Medicine, March 25-29, 2025, Hotel Petrarca, Euganean Thermae, Italy: Program and Abstracts.European journal of translational myology · 2025Article
- Analysis of SMN protein in umbilical cord blood and postnatal peripheral blood of neonates with SMA: a rationale for prompt treatment initiation to prevent SMA development.Orphanet journal of rare diseases · 2025Article
- [Research progress on phenotypic modifier genes in spinal muscular atrophy].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Review
- Skeletal Muscle Mitochondrial and Autophagic Dysregulation Are Modifiable in Spinal Muscular Atrophy.Journal of cachexia, sarcopenia and muscle · 2025Article
- SMN depletion impairs skeletal muscle formation and maturation in a mouse model of SMA.Human molecular genetics · 2025Article
- Characterization of SMA type II skeletal muscle from treated patients shows OXPHOS deficiency and denervation.JCI insight · 2024Article
- Alx3 deficiency disrupts energy homeostasis, alters body composition, and impairs hypothalamic regulation of food intake.Cellular and molecular life sciences : CMLS · 2024Article
- Loss of Calpain 3 dysregulates store-operated calcium entry and its exercise response in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Recent Progress in Gene-Targeting Therapies for Spinal Muscular Atrophy: Promises and Challenges.Genes · 2024Review
- Beyond Contractures in Spinal Muscular Atrophy: Identifying Lower-Limb Joint Hypermobility.Journal of clinical medicine · 2024Article
- Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Paucity of the survival motor neuron (SMN) protein triggers the oft-fatal infantile-onset motor neuron disorder, spinal muscular atrophy (SMA). Augmenting the protein is one means of treating SMA and recently led to FDA approval of an intrathecally delivered SMN-enhancing oligonucleotide currently in use. Notwithstanding the advent of this and other therapies for SMA, it is unclear whether the paralysis associated with the disease derives solely from dysfunctional motor neurons that may be efficiently targeted by restricted delivery of SMN-enhancing agents to the nervous system, or stems from broader defects of the motor unit, arguing for systemic SMN repletion. We investigated the disease-contributing effects of low SMN in one relevant peripheral organ - skeletal muscle - by selectively depleting the protein in only this tissue. We found that muscle deprived of SMN was profoundly damaged. Although a disease phenotype was not immediately obvious, persistent low levels of the protein eventually resulted in muscle fiber defects, neuromuscular junction abnormalities, compromised motor performance, and premature death. Importantly, restoring SMN after the onset of muscle pathology reversed disease. Our results provide the most compelling evidence yet for a direct contributing role of muscle in SMA and argue that an optimal therapy for the disease must be designed to treat this aspect of the dysfunctional motor unit.
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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.