ArticleAnnals of neurology2022
Partial Restoration of Brain Dystrophin and Behavioral Deficits by Exon Skipping in the Muscular Dystrophy X-Linked (mdx) Mouse.
Article in Annals of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Neurological impairments in Duchenne muscular dystrophy: A comprehensive review.Acta neurologica Belgica · 2026Review
- Beyond muscle: Delivering RNA therapeutics to the CNS in Duchenne muscular dystrophy.Journal of neuromuscular diseases · 2026Review
- From molecular correction to functional rescue: delivery, tissue state, and immunobiology as the principal constraints on dystrophin-restoring therapy in Duchenne muscular dystrophy.Frontiers in pharmacology · 2026Review
- Article
- Behavioral improvement in dystrophicMolecular therapy. Nucleic acids · 2025Article
- Ineffective behavioral rescue despite partial brain Dp427 restoration by AAV9-U7-mediated exon 51 skipping inMolecular therapy. Nucleic acids · 2025Article
- Conditional Dmd ablation in muscle and brain causes profound effects on muscle function and neurobehavior.Communications biology · 2025Article
- Progress and prospects in antisense oligonucleotide-mediated exon skipping therapies for Duchenne muscular dystrophy.Journal of muscle research and cell motility · 2025Review
- Understanding Duchenne muscular dystrophy-associated brain pathology.Disease models & mechanisms · 2025Review
- Living with Duchenne Muscular Dystrophy Beyond the Physical Implications: Cognitive Features, Psychopathology Aspects, and Psychosocial Resources-A Narrative Review.Brain sciences · 2025Review
- Impact of distinct dystrophin gene mutations on behavioral phenotypes of Duchenne muscular dystrophy.Disease models & mechanisms · 2024Article
- The bench to bedside journey of tricyclo-DNA antisense oligonucleotides for the treatment of Duchenne muscular dystrophy.RSC medicinal chemistry · 2024Review
- Article
- Therapeutic approaches for Duchenne muscular dystrophy.Nature reviews. Drug discovery · 2023Review
- Partial restoration of brain dystrophin by tricyclo-DNA antisense oligonucleotides alleviates emotional deficits inMolecular therapy. Nucleic acids · 2023Article
- The unconditioned fear response in dystrophin-deficient mice is associated with adrenal and vascular function.Scientific reports · 2023Article
- Investigating the Impact of Delivery Routes for Exon Skipping Therapies in the CNS of DMD Mouse Models.Cells · 2023Article
- Considerations in the Preclinical Assessment of the Safety of Antisense Oligonucleotides.Nucleic acid therapeutics · 2023Review
- Abnormal Expression of Synaptic and Extrasynaptic GABAInternational journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesDuchenne muscular dystrophy is associated with various degrees of cognitive impairment and behavioral disturbances. Emotional and memory deficits also constitute reliable outcome measures to assess efficacy of treatments in the mdx mouse lacking the muscle and neuronal full-length dystrophins. The present study aimed to evaluate whether these deficits could be alleviated by the restoration of brain dystrophin.
methodsWe performed intracerebroventricular administration of a new potent tricyclo-DNA antisense oligonucleotide (tcDNA-ASO) containing a full phosphodiester backbone conjugated to a palmitic acid moiety (tcDNA-ASO), designed to skip the mutated exon 23 of mdx mice.
resultsWe first show that the tcDNA-ASO rescues expression of brain dystrophin to 10-30% of wild-type levels and significantly reduces the abnormal unconditioned fear responses in mdx mice in a dose-dependent manner, 5 weeks post-injection. Exon skipping efficiency, ASO biodistribution, protein restoration and effect on the fear response were optimal with a dose of 400 μg at 6-7 weeks post-injection, with synaptic-like expression in brain tissues such as the hippocampus and amygdala. Furthermore, this dose of tcDNA-ASO restored long-term memory retention of mdx mice in an object recognition task, but only had minor effects on fear conditioning.
interpretationThese results suggest for the first time that postnatal re-expression of brain dystrophin could reverse or at least alleviate some cognitive deficits associated with Duchenne muscular dystrophy. ANN NEUROL 2022;92:213-229.
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