ArticleBrain : a journal of neurology2023
Promyelinating drugs promote functional recovery in an autism spectrum disorder mouse model of Pitt-Hopkins syndrome.
Article in Brain : a journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Beyond Histamine Blockade: Clemastine Fumarate as a Promoter of Myelin Regeneration, Inflammatory Regulation, and Neuroimmune Modulation in CNS Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Review
- In Situ Photo‑Crosslinked Functional Bilayer Hydrogel Modulates Local Microenvironment and Remyelination After Optic Nerve Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Developmental Deficiency of Oligodendrocytes and Myelination in the Central Nervous System of the Fetal Alcohol Syndrome Mouse Model.CNS neuroscience & therapeutics · 2026Article
- Myelin, white matter, and social deficits in autism spectrum disorder.Neural regeneration research · 2026Article
- Myelin dysfunction in autism spectrum disorder: insights into core symptoms and mechanisms of brain development.Molecular psychiatry · 2026Review
- Shank3 related oligodendrocyte alterations in autism are restored by Erk pathway inhibition.Molecular psychiatry · 2026Article
- Myelination across the autism spectrum: therapeutic targeting of the oligodendrocyte lineage and myelination defects.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Juvenile reinstatement of TCF4 in Pitt-Hopkins syndrome model mice reveals a critical window for genetic intervention.bioRxiv : the preprint server for biology · 2025Article
- Decomposing genetic effects of social connectedness and depression on youth behaviors and long-term clinical outcomes.medRxiv : the preprint server for health sciences · 2025Article
- Central thyroid hormone receptor-beta: Sensitivity to alcohol and a role in regulating alcohol drinking.Hormones and behavior · 2025Article
- A novel human organoid model system reveals requirement of TCF4 for oligodendroglial differentiation.Life science alliance · 2025Article
- Oxytocin enhances oligodendrocyte development and improves social deficits in autistic rats.Frontiers in neuroscience · 2025Article
- Neuroprotective Effect of Clemastine Improved Oligodendrocyte Proliferation through the MAPK/ERK Pathway in a Neonatal Hypoxia Ischemia Rat Model.International journal of molecular sciences · 2024Article
- Functional myelin in cognition and neurodevelopmental disorders.Cellular and molecular life sciences : CMLS · 2024Review
- Transcription factor 4 expression in the developing non-human primate brain: a comparative analysis with the mouse brain.Frontiers in neuroanatomy · 2024Article
- The missing hallmark of health: psychosocial adaptation.Cell stress · 2024Article
- Insights on therapeutic potential of clemastine in neurological disorders.Frontiers in molecular neuroscience · 2023Review
- Utilizing hiPSC-derived oligodendrocytes to study myelin pathophysiology in neuropsychiatric and neurodegenerative disorders.Frontiers in cellular neuroscience · 2023Review
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Authors and funding
12 authors at 4 institutions in 1 country.
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Abstract
Pitt-Hopkins syndrome is an autism spectrum disorder caused by autosomal dominant mutations in the human transcription factor 4 gene (TCF4). One pathobiological process caused by murine Tcf4 mutation is a cell autonomous reduction in oligodendrocytes and myelination. In this study, we show that the promyelinating compounds, clemastine, sobetirome and Sob-AM2 are effective at restoring myelination defects in a Pitt-Hopkins syndrome mouse model. In vitro, clemastine treatment reduced excess oligodendrocyte precursor cells and normalized oligodendrocyte density. In vivo, 2-week intraperitoneal administration of clemastine also normalized oligodendrocyte precursor cell and oligodendrocyte density in the cortex of Tcf4 mutant mice and appeared to increase the number of axons undergoing myelination, as EM imaging of the corpus callosum showed a significant increase in the proportion of uncompacted myelin and an overall reduction in the g-ratio. Importantly, this treatment paradigm resulted in functional rescue by improving electrophysiology and behaviour. To confirm behavioural rescue was achieved via enhancing myelination, we show that treatment with the thyroid hormone receptor agonist sobetirome or its brain penetrating prodrug Sob-AM2, was also effective at normalizing oligodendrocyte precursor cell and oligodendrocyte densities and behaviour in the Pitt-Hopkins syndrome mouse model. Together, these results provide preclinical evidence that promyelinating therapies may be beneficial in Pitt-Hopkins syndrome and potentially other neurodevelopmental disorders characterized by dysmyelination.
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