ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
PTEN depletion decreases disease severity and modestly prolongs survival in a mouse model of spinal muscular atrophy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 3 of them syntheses 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
33 citing papers in PubMed, 3 syntheses or guidelines pooled it, 52 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
- Drug treatment for spinal muscular atrophy types II and III.The Cochrane database of systematic reviews · 2020Pooled it
- Drug treatment for spinal muscular atrophy type I.The Cochrane database of systematic reviews · 2019Pooled it
- Cardiac defects in spinal muscular atrophy and the role of SMN in cardiomyocyte homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Treating neuromuscular diseases: unveiling gene therapy breakthroughs and pioneering future applications.Journal of biomedical science · 2025Review
- Redox Regulation of PTEN by Reactive Oxygen Species: Its Role in Physiological Processes.Antioxidants (Basel, Switzerland) · 2024Review
- Optimization of base editors for the functional correction of SMN2 as a treatment for spinal muscular atrophy.Nature biomedical engineering · 2024Article
- Diabetic Polyneuropathy: New Strategies to Target Sensory Neurons in Dorsal Root Ganglia.International journal of molecular sciences · 2023Review
- Digital color-coded molecular barcoding reveals dysregulation of common FUS and FMRP targets in soma and neurites of ALS mutant motoneurons.Cell death discovery · 2023Article
- ABT1 modifies SMARD1 pathology via interactions with IGHMBP2 and stimulation of ATPase and helicase activity.JCI insight · 2023Article
- Bisperoxovanadium promotes motor neuron survival and neuromuscular innervation in amyotrophic lateral sclerosis.Molecular brain · 2021Article
- The Importance of Digging into the Genetics ofInternational journal of molecular sciences · 2021Review
- Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine.Cell reports. Medicine · 2021Review
- SMN protein promotes membrane compartmentalization of ribosomal protein S6 transcript in human fibroblasts.Scientific reports · 2020Article
- A Single Amino Acid Residue Regulates PTEN-Binding and Stability of the Spinal Muscular Atrophy Protein SMN.Cells · 2020Article
- The Need for SMN-Independent Treatments of Spinal Muscular Atrophy (SMA) to Complement SMN-Enhancing Drugs.Frontiers in neurology · 2020Review
- AAV9-mediated delivery of miR-23a reduces disease severity in Smn2B/-SMA model mice.Human molecular genetics · 2019Article
- AAV9 Vector: a Novel modality in gene therapy for spinal muscular atrophy.Gene therapy · 2019Review
- Diabetic neuropathy and the sensory neuron: New aspects of pathogenesis and their treatment implications.Journal of diabetes investigation · 2018Review
- Molecular Factors Involved in Spinal Muscular Atrophy Pathways as Possible Disease-modifying Candidates.Current genomics · 2018Review
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 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinal muscular atrophy (SMA) is the second most common genetic cause of death in childhood. However, no effective treatment is available to halt disease progression. SMA is caused by mutations in the survival motor neuron 1 (SMN1) gene. We previously reported that PTEN depletion leads to an increase in survival of SMN-deficient motor neurons. Here, we aimed to establish the impact of PTEN modulation in an SMA mouse model in vivo. Initial experiments using intramuscular delivery of adeno-associated vector serotype 6 (AAV6) expressing shRNA against PTEN in an established mouse model of severe SMA (SMNΔ7) demonstrated the ability to ameliorate the severity of neuromuscular junction pathology. Subsequently, we developed self-complementary AAV9 expressing siPTEN (scAAV9-siPTEN) to allow evaluation of the effect of systemic suppression of PTEN on the disease course of SMA in vivo. Treatment with a single injection of scAAV9-siPTEN at postnatal day 1 resulted in a modest threefold extension of the lifespan of SMNΔ7 mice, increasing mean survival to 30 days, compared to 10 days in untreated mice. Our data revealed that systemic PTEN depletion is an important disease modifier in SMNΔ7 mice, and therapies aimed at lowering PTEN expression may therefore offer a potential therapeutic strategy for SMA.
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.