ArticleHuman molecular genetics2014
Widespread spinal cord transduction by intrathecal injection of rAAV delivers efficacious RNAi therapy for amyotrophic lateral sclerosis.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed.
- First-in-human trial of blood-brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound.Nature communications · 2019Trial
- Antisense oligonucleotide treatment following viral delivery of artificial SOD1-targeting miRNA shows improved efficacy in SOD1-G93A mice.Molecular therapy. Advances · 2026Article
- The Prospective Regulatory Functions of lncRNAs and Their ceRNA Networks in the Development of Motor Neurons and Associated Diseases.Biomolecules · 2026Review
- Intravenous administration of an engineered AAV9-gene-silencing vector suppresses human SOD1 and extends survival in an ALS mouse model.Nature communications · 2026Article
- Targeting Neurovascular Pathways: Gene Therapy as a Novel Treatment for Vascular Dementia After Stroke.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Review
- Intrathecal delivery of AAVrh10-mHexa combined with anti-inflammatory treatment reduces neuropathological markers and extends the lifespan of mice with early-onset Tay-Sachs disease.Metabolic brain disease · 2026Article
- Gene Therapy of Adrenomyeloneuropathy: Challenges, Target Cells, and Prospectives.Biomedicines · 2025Review
- Targets and Gene Therapy of ALS (Part 1).International journal of molecular sciences · 2025Review
- Dorsal root ganglion toxicity after AAV intra-CSF delivery of a RNAi expression construct into non-human primates and mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- In vivo and ex vivo gene therapy for neurodegenerative diseases: a promise for disease modification.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Review
- Efficacy and safety of a SOD1-targeting artificial miRNA delivered by AAV9 in mice are impacted by miRNA scaffold selection.Molecular therapy. Nucleic acids · 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
- A Minimally-Invasive Method for Serial Cerebrospinal Fluid Collection and Injection in Rodents with High Survival Rates.Biomedicines · 2023Article
- In vivo genome editing using novel AAV-PHP variants rescues motor function deficits and extends survival in a SOD1-ALS mouse model.Gene therapy · 2023Article
- Gene Therapy in ALS and SMA: Advances, Challenges and Perspectives.International journal of molecular sciences · 2023Review
- Approaches to Gene Modulation Therapy for ALS.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Targeted gene silencing in the nervous system with CRISPR-Cas13.Science advances · 2022Article
- Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases.Molecular neurobiology · 2022Review
- RNA Deregulation in Amyotrophic Lateral Sclerosis: The Noncoding Perspective.International journal of molecular sciences · 2021Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) causes motor neuron degeneration and paralysis. No treatment can significantly slow or arrest the disease progression. Mutations in the SOD1 gene cause a subset of familial ALS by a gain of toxicity. In principle, these cases could be treated with RNAi that destroys the mutant mRNA, thereby abolishing the toxic protein. However, no system is available to efficiently deliver the RNAi therapy. Recombinant adenoassociated virus (rAAV) is a promising vehicle due to its long-lasting gene expression and low toxicity. However, ALS afflicts broad areas of the central nervous system (CNS). A lack of practical means to spread rAAV broadly has hindered its application in treatment of ALS. To overcome this barrier, we injected several rAAV serotypes into the cerebrospinal fluid. We found that some rAAV serotypes such as rAAVrh10 and rAAV9 transduced cells throughout the length of the spinal cord following a single intrathecal injection and in the broad forebrain following a single injection into the third ventricle. Furthermore, a single intrathecal injection of rAAVrh10 robustly transduced motor neurons throughout the spinal cord in a non-human primate. These results suggested a therapeutic potential of this vector for ALS. To test this, we injected a rAAVrh10 vector that expressed an artificial miRNA targeting SOD1 into the SOD1G93A mice. This treatment knocked down the mutant SOD1 expression and slowed the disease progression. Our results demonstrate the potential of rAAVs for delivering gene therapy to treat ALS and other diseases that afflict broad areas of the CNS.
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