ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
Adeno-associated virus-mediated delivery of a recombinant single-chain antibody against misfolded superoxide dismutase for treatment of amyotrophic lateral sclerosis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Antibody-Based Therapeutic Interventions for Amyotrophic Lateral Sclerosis: A Systematic Literature Review.Frontiers in neuroscience · 2021Pooled it
- Novel Gene Therapy Approaches for Targeting Neurodegenerative Disorders: Focusing on Delivering Neurotrophic Genes.Molecular neurobiology · 2025Review
- Targeting cytokine networks in neuroinflammatory diseases.Nature reviews. Drug discovery · 2024Review
- 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 novel antibody to treat SOD1-related amyotrophic lateral sclerosis.Molecular therapy. Methods & clinical development · 2023Article
- Efficacy of oligodendrocyte precursor cells as delivery vehicles for single-chain variable fragment to misfolded SOD1 in ALS rat model.Molecular therapy. Methods & clinical development · 2023Article
- Anti-SOD1 Nanobodies That Stabilize Misfolded SOD1 Proteins Also Promote Neurite Outgrowth in Mutant SOD1 Human Neurons.International journal of molecular sciences · 2022Article
- Blood-Brain Barrier Disruption and Its Involvement in Neurodevelopmental and Neurodegenerative Disorders.International journal of molecular sciences · 2022Review
- Approaches to Gene Modulation Therapy for ALS.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Autologous treatment for ALS with implication for broad neuroprotection.Translational neurodegeneration · 2022Article
- Gene Transfer of Skeletal Muscle-Type Myosin Light Chain Kinase via Adeno-Associated Virus 6 Improves Muscle Functions in an Amyotrophic Lateral Sclerosis Mouse Model.International journal of molecular sciences · 2022Article
- Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases.Molecular neurobiology · 2022Review
- AAV Vector-Mediated Antibody Delivery (A-MAD) in the Central Nervous System.Frontiers in neurology · 2022Review
- Prionoids in amyotrophic lateral sclerosis.Brain communications · 2022Review
- Gene therapy for ALS: A review.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Vectored Immunotherapeutics for Infectious Diseases: Can rAAVs Be The Game Changers for Fighting Transmissible Pathogens?Frontiers in immunology · 2021Review
- Combinations of Single Chain Variable Fragments From HIV Broadly Neutralizing Antibodies Demonstrate High Potency and Breadth.Frontiers in immunology · 2021Article
- Treating Parkinson's Disease with Antibodies: Previous Studies and Future Directions.Journal of Parkinson's disease · 2021Review
- Monoclonal full-length antibody against TAR DNA binding protein 43 reduces related proteinopathy in neurons.JCI insight · 2020Article
- Defining novel functions for cerebrospinal fluid in ALS pathophysiology.Acta neuropathologica communications · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
There is emerging evidence that the misfolding of superoxide dismutase 1 (SOD1) may represent a common pathogenic event in both familial and sporadic amyotrophic lateral sclerosis (ALS). To reduce the burden of misfolded SOD1 species in the nervous system, we have tested a novel therapeutic approach based on adeno-associated virus (AAV)-mediated tonic expression of a DNA construct encoding a secretable single-chain fragment variable (scFv) antibody composed of the variable heavy and light chain regions of a monoclonal antibody (D3H5) binding specifically to misfolded SOD1. A single intrathecal injection of the AAV encoding the single-chain antibody in SOD1(G93A) mice at 45 days of age resulted in sustained expression of single-chain antibodies in the spinal cord, and it delayed disease onset and extension of life span by up to 28%, in direct correlation with scFv titers in the spinal cord. The treatment caused attenuation of neuronal stress signals and reduction in levels of misfolded SOD1 in the spinal cord of SOD1(G93A) mice. From these results, we propose that an immunotherapy based on intrathecal inoculation of AAV encoding a secretable scFv against misfolded SOD1 should be considered as potential treatment for ALS, especially for individuals carrying SOD1 mutations.
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