ArticleAnnals of clinical and translational neurology2022
Guanabenz ameliorates disease in vanishing white matter mice in contrast to sephin1.
Article in Annals of clinical and translational neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- Pediatric pharmacokinetics and pharmacodynamics of guanabenz for the treatment of vanishing white matter.Scientific reports · 2026Article
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Cell-specific Eif2b5 mutant mice: novel insights into roles of macroglia in vanishing white matter.Brain : a journal of neurology · 2025Article
- The impact of vanishing white matter on unaffected family members.Orphanet journal of rare diseases · 2025Article
- An atypical initial revelation of CACH-vanishing white matter syndrome miming herpetic encephalitis in a 6-year-old child: Case report and brief review.Radiology case reports · 2025Article
- ISR Modulators in Neurological Diseases.Current neuropharmacology · 2025Review
- A Rare Case of Vanishing White Matter Disease.Cureus · 2024Article
- Mammalian integrated stress responses in stressed organelles and their functions.Acta pharmacologica Sinica · 2024Review
- In vivo base editing of a pathogenic Eif2b5 variant improves vanishing white matter phenotypes in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Pridopidine subtly ameliorates motor skills in a mouse model for vanishing white matter.Life science alliance · 2024Article
- Lithium: effects in animal models of vanishing white matter are not promising.Frontiers in neuroscience · 2024Article
- Core protocol development for phase 2/3 clinical trials in the leukodystrophy vanishing white matter: a consensus statement by the VWM consortium and patient advocates.BMC neurology · 2023Article
- Secretomics Alterations and Astrocyte Dysfunction in Human iPSC of Leukoencephalopathy with Vanishing White Matter.Neurochemical research · 2022Article
- Guanabenz ameliorates disease in vanishing white matter mice in contrast to sephin1.Annals of clinical and translational neurology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveVanishing white matter (VWM) is a leukodystrophy, characterized by stress-sensitive neurological deterioration and premature death. It is currently without curative treatment. It is caused by bi-allelic pathogenic variants in the genes encoding eukaryotic initiation factor 2B (eIF2B). eIF2B is essential for the regulation of the integrated stress response (ISR), a physiological response to cellular stress. Preclinical studies on VWM mouse models revealed that deregulated ISR is key in the pathophysiology of VWM and an effective treatment target. Guanabenz, an α2-adrenergic agonist, attenuates the ISR and has beneficial effects on VWM neuropathology. The current study aimed at elucidating guanabenz's disease-modifying potential and mechanism of action in VWM mice. Sephin1, an ISR-modulating guanabenz analog without α2-adrenergic agonistic properties, was included to separate effects on the ISR from α2-adrenergic effects.
methodsWild-type and VWM mice were subjected to placebo, guanabenz or sephin1 treatments. Effects on clinical signs, neuropathology, and ISR deregulation were determined. Guanabenz's and sephin1's ISR-modifying effects were tested in cultured cells that expressed or lacked the α2-adrenergic receptor.
resultsGuanabenz improved clinical signs, neuropathological hallmarks, and ISR regulation in VWM mice, but sephin1 did not. Guanabenz's effects on the ISR in VWM mice were not replicated in cell cultures and the contribution of α2-adrenergic effects on the deregulated ISR could therefore not be assessed.
interpretationGuanabenz proved itself as a viable treatment option for VWM. The exact mechanism through which guanabenz exerts its ameliorating impact on VWM requires further studies. Sephin1 is not simply a guanabenz replacement without α2-adrenergic effects.
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