ArticleGene therapy2022
Central and peripheral delivered AAV9-SMN are both efficient but target different pathomechanisms in a mouse model of spinal muscular atrophy.
Article in Gene therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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
16 citing papers in PubMed, 23 citations in OpenAlex.
- Tumor-Secreted ADAMTSL4 Activates Latent TGFβ1 to Drive Cancer Cachexia.Cancer discovery · 2026Article
- Maternal-Fetal Administration of Risdiplam Partially Rescues the SMNΔ7 Mouse Model of Spinal Muscular Atrophy.Annals of neurology · 2026Article
- Lack of sensorimotor toxicity when using the clinical SMN expression cassette in scAAV9.Nature neuroscience · 2026Article
- Spinal muscular atrophy: Biology, pathogenesis, and therapeutic advances.Therapeutic advances in neurological disorders · 2026Review
- Mifepristone alone and in combination with scAAV9-SMN1 gene therapy improves disease phenotypes in SmnScientific reports · 2025Article
- Cerebellar defects are a primary pathology in mouse models of spinal muscular atrophy.Brain pathology (Zurich, Switzerland) · 2025Article
- 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
- Article
- Peripheral defects precede neuromuscular pathology in theJournal of neuromuscular diseases · 2024Article
- Neurofilaments as biomarkers in neurological disorders - towards clinical application.Nature reviews. Neurology · 2024Review
- Long term peripheral AAV9-SMN gene therapy promotes survival in a mouse model of spinal muscular atrophy.Human molecular genetics · 2024Article
- Optimization of base editors for the functional correction of SMN2 as a treatment for spinal muscular atrophy.Nature biomedical engineering · 2024Article
- Cerebellar structural, astrocytic, and neuronal abnormalities in the SMNΔ7 mouse model of spinal muscular atrophy.Brain pathology (Zurich, Switzerland) · 2023Article
- ABT1 modifies SMARD1 pathology via interactions with IGHMBP2 and stimulation of ATPase and helicase activity.JCI insight · 2023Article
- Suppression of the necroptotic cell death pathways improves survival inFrontiers in cellular neuroscience · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinal muscular atrophy (SMA) is a neuromuscular disease caused by loss of the SMN1 gene and low SMN protein levels. Although lower motor neurons are a primary target, there is evidence that peripheral organ defects contribute to SMA. Current SMA gene therapy and clinical trials use a single intravenous bolus of the blood-brain-barrier penetrant scAAV9-cba-SMN by either systemic or central nervous system (CNS) delivery, resulting in impressive amelioration of the clinical phenotype but not a complete cure. The impact of scAAV9-cba-SMN treatment regimens on the CNS as well as on specific peripheral organs is yet to be described in a comparative manner. Therefore, we injected SMA mice with scAAV9-cba-SMN either intravenously (IV) for peripheral SMN restoration or intracerebroventricularly (ICV) for CNS-focused SMN restoration. In our system, ICV injections increased SMN in peripheral organs and the CNS while IV administration increased SMN in peripheral tissues only, largely omitting the CNS. Both treatments rescued several peripheral phenotypes while only ICV injections were neuroprotective. Surprisingly, both delivery routes resulted in a robust rescue effect on survival, weight, and motor function, which in IV-treated mice relied on peripheral SMN restoration but not on targeting the motor neurons. This demonstrates the independent contribution of peripheral organs to SMA pathology and suggests that treatments should not be restricted to motor neurons.
Indexed as
Identifiers
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.