ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Delayed disease onset and extended survival in the SOD1G93A rat model of amyotrophic lateral sclerosis after suppression of mutant SOD1 in the motor cortex.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 132 citations in OpenAlex.
- First-in-human trial of blood-brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound.Nature communications · 2019Trial
- Lateral sclerosis in amyotrophic lateral sclerosis is an upper motor neuron distal axonopathy ("dying back"): a clinical-neuropathological study.Acta neuropathologica · 2026Article
- RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Safety and efficacy evaluation of intracerebroventricular human neural stem cell transplantation in SOD1 mice as a novel approach for ALS.Journal of translational medicine · 2025Article
- Targets and Gene Therapy of ALS (Part 1).International journal of molecular sciences · 2025Review
- Methodological and analytical limitations undermine reported outcomes of spinal DC stimulation in ALS.Frontiers in neurology · 2025Article
- Amyotrophic Lateral Sclerosis: Insights and New Prospects in Disease Pathophysiology, Biomarkers and Therapies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- In vivo and ex vivo gene therapy for neurodegenerative diseases: a promise for disease modification.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Cell therapy for neurological disorders.Nature medicine · 2024Review
- Combination AAV therapy with galectin-1 and SOD1 downregulation demonstrates superior therapeutic effect in a severe ALS mouse model.Molecular therapy. Methods & clinical development · 2024Article
- Molecular mechanisms and therapeutic strategies for neuromuscular diseases.Cellular and molecular life sciences : CMLS · 2024Review
- Current potential therapeutics of amyotrophic lateral sclerosis.Frontiers in neurology · 2024Review
- Human iPSC-derived neural progenitor cells secreting GDNF provide protection in rodent models of ALS and retinal degeneration.Stem cell reports · 2023Article
- Novel rAAV vector mediated intrathecal HGF delivery has an impact on neuroimmune modulation in the ALS motor cortex with TDP-43 pathology.Gene therapy · 2023Article
- Review
- Remodeling of astrocyte secretome in amyotrophic lateral sclerosis: uncovering novel targets to combat astrocyte-mediated toxicity.Translational neurodegeneration · 2022Review
- Approaches to Gene Modulation Therapy for ALS.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Gene Therapy in Amyotrophic Lateral Sclerosis.Cells · 2022Review
- Enhanced Cortical Metabolic Activity in Females and Males of a Slow Progressing Mouse Model of Amyotrophic Lateral Sclerosis.Neurochemical research · 2022Article
- Imaging Net Retrograde Axonal Transport In Vivo: A Physiological Biomarker.Annals of neurology · 2022Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Sporadic amyotrophic lateral sclerosis (ALS) is a fatal disease with unknown etiology, characterized by a progressive loss of motor neurons leading to paralysis and death typically within 3-5 years of onset. Recently, there has been remarkable progress in understanding inherited forms of ALS in which well defined mutations are known to cause the disease. Rodent models in which the superoxide dismutase-1 (SOD1) mutation is overexpressed recapitulate hallmark signs of ALS in patients. Early anatomical changes in mouse models of fALS are seen in the neuromuscular junctions (NMJs) and lower motor neurons, and selective reduction of toxic mutant SOD1 in the spinal cord and muscle of these models has beneficial effects. Therefore, much of ALS research has focused on spinal motor neuron and NMJ aspects of the disease. Here we show that, in the SOD1(G93A) rat model of ALS, spinal motor neuron loss occurs presymptomatically and before degeneration of ventral root axons and denervation of NMJs. Although overt cell death of corticospinal motor neurons does not occur until disease endpoint, we wanted to establish whether the upper motor neuron might still play a critical role in disease progression. Surprisingly, the knockdown of mutant SOD1 in only the motor cortex of presymptomatic SOD1(G93A) rats through targeted delivery of AAV9-SOD1-shRNA resulted in a significant delay of disease onset, expansion of lifespan, enhanced survival of spinal motor neurons, and maintenance of NMJs. This datum suggests an early dysfunction and thus an important role of the upper motor neuron in this animal model of ALS and perhaps patients with the disease.
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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.