ArticleAnnals of clinical and translational neurology2020
Vorinostat in the acute neuroinflammatory form of X-linked adrenoleukodystrophy.
Article in Annals of clinical and translational neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Post-translational modifications in Neuroimmune cells during neuroinflammation: integrated regulatory networks and therapeutic opportunities.Biology direct · 2026Review
- Inflammation and Immunomodulation in Cerebral X-linked Adrenoleukodystrophy: Review of Pathology and Interventions.Journal of child neurology · 2026Review
- Efficacy of HDAC Inhibitors in Driving Peroxisomal β-Oxidation and Immune Responses in Human Macrophages: Implications for Neuroinflammatory Disorders.Biomolecules · 2023Article
- Peroxisome disruption alters lipid metabolism and potentiates antitumor response with MAPK-targeted therapy in melanoma.The Journal of clinical investigation · 2023Article
- A gene regulatory network approach harmonizes genetic and epigenetic signals and reveals repurposable drug candidates for multiple sclerosis.Human molecular genetics · 2023Article
- Human-Induced Pluripotent Stem Cell-Based Model of the Blood-Brain at 10 Years: A Retrospective on Past and Current Disease Models.Handbook of experimental pharmacology · 2023Review
- Saturated very long-chain fatty acids regulate macrophage plasticity and invasiveness.Journal of neuroinflammation · 2022Article
- Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania.International journal of neonatal screening · 2022Article
- The Role of Oxidative Stress and Inflammation in X-Link Adrenoleukodystrophy.Frontiers in nutrition · 2022Review
- Repurposing Vorinostat for the Treatment of Disorders Affecting Brain.Neuromolecular medicine · 2021Review
- Drug discovery for X-linked adrenoleukodystrophy: An unbiased screen for compounds that lower very long-chain fatty acids.Journal of cellular biochemistry · 2021Article
- Peroxisomal ABC Transporters: An Update.International journal of molecular sciences · 2021Review
- Targeting foam cell formation in inflammatory brain diseases by the histone modifier MS-275.Annals of clinical and translational neurology · 2020Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
objectiveTo identify a pharmacological compound targeting macrophages, the most affected immune cells in inflammatory X-linked adrenoleukodystrophy (cerebral X-ALD) caused by ABCD1 mutations and involved in the success of hematopoietic stem cell transplantation and gene therapy.
methodsA comparative database analysis elucidated the epigenetic repressing mechanism of the related ABCD2 gene in macrophages and identified the histone deacetylase (HDAC) inhibitor Vorinostat as a compound to induce ABCD2 in these cells to compensate for ABCD1 deficiency. In these cells, we investigated ABCD2 and pro-inflammatory gene expression, restoration of defective peroxisomal β-oxidation activity, accumulation of very long-chain fatty acids (VLCFAs) and their differentiation status. We investigated ABCD2 and pro-inflammatory gene expression, restoration of defective peroxisomal ß-oxidation activity, accumulation of very long-chain fatty acids (VLCFA) and differentiation status. Three advanced cerebral X-ALD patients received Vorinostat and CSF and MRI diagnostics was carried out in one patient after 80 days of treatment.
resultsVorinostat improved the metabolic defects in X-ALD macrophages by stimulating ABCD2 expression, peroxisomal ß-oxidation, and ameliorating VLCFA accumulation. Vorinostat interfered with pro-inflammatory skewing of X-ALD macrophages by correcting IL12B expression and further reducing monocyte differentiation. Vorinostat normalized the albumin and immunoglobulin CSF-serum ratios, but not gadolinium enhancement upon 80 days of treatment.
interpretationThe beneficial effects of HDAC inhibitors on macrophages in X-ALD and the improvement of the blood-CSF/blood-brain barrier are encouraging for future investigations. In contrast with Vorinostat, less toxic macrophage-specific HDAC inhibitors might improve also the clinical state of X-ALD patients with advanced inflammatory demyelination.
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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.