Trial reportThe Journal of clinical investigation2019
Age-dependent SMN expression in disease-relevant tissue and implications for SMA treatment.
Trial report in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 187 citations in OpenAlex.
- Swallowing and feeding after disease-modifying treatment for spinal muscular atrophy: a systematic review of assessment modalities and outcomes.Orphanet journal of rare diseases · 2026Pooled it
- Article
- Targeted knockdown of Smn in muscle stem cells induces non-cell autonomous loss of motor neurons.Brain : a journal of neurology · 2026Article
- Ten years of disease-modifying therapy in spinal muscular atrophy: lessons learned and future directions.Nature reviews. Neurology · 2026Review
- Maternal-Fetal Administration of Risdiplam Partially Rescues the SMNΔ7 Mouse Model of Spinal Muscular Atrophy.Annals of neurology · 2026Article
- Survival Motor Neuron Protein Requirement-Supply Mismatch in Spinal Muscular Atrophy: A Conceptual Framework.Advances in therapy · 2026Review
- Disease-Modifying Therapies in Spinal Muscular Atrophy: Neurodevelopmental and Behavioral Outcomes in the Treatment Era.Advances in therapy · 2026Review
- Characterisation of the SMN1/2 locus using a highly specific variant caller on whole-genome sequence data from 500,000 individuals.European journal of human genetics : EJHG · 2026Article
- Onasemnogene abeparvovec gene therapy for treatment of patients with spinal muscular atrophy: Updated real-world practical considerations.Journal of neuromuscular diseases · 2026Review
- In Utero Molecular-Targeted Drug Therapies: Translational Principles, Pharmacologic Considerations, and Emerging Clinical Applications.Journal of clinical medicine · 2026Review
- The Expanding Role of Gene Sequencing in Shaping Fetal Therapies: Clinical and Ethical Considerations.Prenatal diagnosis · 2026Review
- RNA biomarkers in spinal muscular atrophy: enhancing pathogenesis understanding and guiding precision medicine.Cellular and molecular life sciences : CMLS · 2026Review
- Cerebellar pathology contributes to neurodevelopmental deficits in spinal muscular atrophy.Brain : a journal of neurology · 2026Article
- Real-world evidence on nusinersen treatment of persons with SMA: a focused review.Journal of neuromuscular diseases · 2026Review
- Spinal muscular atrophy: Biology, pathogenesis, and therapeutic advances.Therapeutic advances in neurological disorders · 2026Review
- Targeted antisense oligonucleotide treatment rescues developmental alterations in spinal muscular atrophy organoids.Nature communications · 2025Article
- Cerebellar defects are a primary pathology in mouse models of spinal muscular atrophy.Brain pathology (Zurich, Switzerland) · 2025Article
- Pharmacokinetics of therapies approved for spinal muscular atrophy: A narrative review of current evidence.The Journal of international medical research · 2025Review
- Prenatal SMN-dependent defects in translation uncover reversible primary cilia phenotypes in spinal muscular atrophy.JCI insight · 2025Article
- Comparative Clinical Outcomes of Nusinersen and Gene Therapy in Spinal Muscular Atrophy Type 1.JAMA network open · 2025Article
54 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
22 authors at 9 institutions in 2 countries.
Funding
Abstract
BACKGROUNDSpinal muscular atrophy (SMA) is caused by deficient expression of survival motor neuron (SMN) protein. New SMN-enhancing therapeutics are associated with variable clinical benefits. Limited knowledge of baseline and drug-induced SMN levels in disease-relevant tissues hinders efforts to optimize these treatments.METHODSSMN mRNA and protein levels were quantified in human tissues isolated during expedited autopsies.RESULTSSMN protein expression varied broadly among prenatal control spinal cord samples, but was restricted at relatively low levels in controls and SMA patients after 3 months of life. A 2.3-fold perinatal decrease in median SMN protein levels was not paralleled by comparable changes in SMN mRNA. In tissues isolated from nusinersen-treated SMA patients, antisense oligonucleotide (ASO) concentration and full-length (exon 7 including) SMN2 (SMN2-FL) mRNA level increases were highest in lumbar and thoracic spinal cord. An increased number of cells showed SMN immunolabeling in spinal cord of treated patients, but was not associated with an increase in whole-tissue SMN protein levels.CONCLUSIONSA normally occurring perinatal decrease in whole-tissue SMN protein levels supports efforts to initiate SMN-inducing therapies as soon after birth as possible. Limited ASO distribution to rostral spinal and brain regions in some patients likely limits clinical response of motor units in these regions for those patients. These results have important implications for optimizing treatment of SMA patients and warrant further investigations to enhance bioavailability of intrathecally administered ASOs.FUNDINGSMA Foundation, SMART, NIH (R01-NS096770, R01-NS062869), Ionis Pharmaceuticals, and PTC Therapeutics. Biogen provided support for absolute real-time RT-PCR.
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What OpenQuestion holds
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.