ArticleThe Journal of biological chemistry2008
Therapeutic gene silencing delivered by a chemically modified small interfering RNA against mutant SOD1 slows amyotrophic lateral sclerosis progression.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 64 citations in OpenAlex.
- CRISPR/Cas9 a genomic engineering technology for treatment in ALS mouse models.Regenerative therapy · 2025Review
- Variability in SOD1-associated amyotrophic lateral sclerosis: geographic patterns, clinical heterogeneity, molecular alterations, and therapeutic implications.Translational neurodegeneration · 2024Review
- Proteostatic imbalance and protein spreading in amyotrophic lateral sclerosis.The EMBO journal · 2021Review
- RNA Dysregulation in Amyotrophic Lateral Sclerosis.Frontiers in genetics · 2018Review
- Polyethylenimine Nanoparticle-Mediated siRNA Delivery to Reduce α-Synuclein Expression in a Model of Parkinson's Disease.Molecular therapy. Nucleic acids · 2017Article
- Motor Neuron Gene Therapy: Lessons from Spinal Muscular Atrophy for Amyotrophic Lateral Sclerosis.Frontiers in molecular neuroscience · 2017Review
- Docosahexaenoic Acid Conjugation Enhances Distribution and Safety of siRNA upon Local Administration in Mouse Brain.Molecular therapy. Nucleic acids · 2016Article
- Adeno-associated virus-delivered artificial microRNA extends survival and delays paralysis in an amyotrophic lateral sclerosis mouse model.Annals of neurology · 2016Article
- Non-Viral Nucleic Acid Delivery Strategies to the Central Nervous System.Frontiers in molecular neuroscience · 2016Review
- Structural Dynamics of Human Argonaute2 and Its Interaction with siRNAs Designed to Target Mutant tdp43.Advances in bioinformatics · 2016Article
- Allele-specific silencing of mutant Ataxin-7 in SCA7 patient-derived fibroblasts.European journal of human genetics : EJHG · 2014Article
- Synthetic immunosurveillance systems: nanodevices to monitor physiological events.Biosensors & bioelectronics · 2014Review
- Widespread spinal cord transduction by intrathecal injection of rAAV delivers efficacious RNAi therapy for amyotrophic lateral sclerosis.Human molecular genetics · 2014Article
- Identification of human monoclonal antibodies specific for human SOD1 recognizing distinct epitopes and forms of SOD1.PloS one · 2013Article
- A high-throughput screen to identify inhibitors of SOD1 transcription.Frontiers in bioscience (Elite edition) · 2012Article
- Research advances in gene therapy approaches for the treatment of amyotrophic lateral sclerosis.Cellular and molecular life sciences : CMLS · 2012Review
- Progress toward in vivo use of siRNAs-II.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Review
- Mutant TDP-43 in motor neurons promotes the onset and progression of ALS in rats.The Journal of clinical investigation · 2012Article
- Rationale for therapeutic silencing of alpha-synuclein in Parkinson's disease.Journal of movement disorders · 2011Review
- Research advances in amyotrophic lateral sclerosis, 2009 to 2010.Current neurology and neuroscience reports · 2011Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
Inherited neurodegenerative diseases, such as Huntington disease and subset of Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis, are caused by the mutant genes that have gained undefined properties that harm cells in the nervous system, causing neurodegeneration and clinical phenotypes. Lowering the mutant gene expression is predicted to slow the disease progression and produce clinical benefit. Administration of small interfering RNA (siRNA) can silence specific genes. However, long term delivery of siRNA to silence the mutant genes, a requirement for treatment of these chronic central nervous system (CNS) diseases, remains a critical unsolved issue. Here we designed and tested a chemically stabilized siRNA against human Cu,Zn-superoxide dismutase (SOD1) in a mouse model for amyotrophic lateral sclerosis. We show that the modified siRNA has enhanced stability and retains siRNA activity. Administration of this siRNA at the disease onset by long term infusion into the CNS resulted in widespread distribution of this siRNA, knocked down the mutant SOD1 expression, slowed the disease progression, and extended the survival. These results bring RNA interference therapy one step closer to its clinical application for treatment of chronic, devastating, and fatal CNS disorders.
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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.