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In these cells, we investigated <jats:italic>ABCD2<\/jats:italic> and pro\u2010inflammatory gene expression, restoration of defective peroxisomal \u03b2\u2010oxidation activity, accumulation of very long\u2010chain fatty acids (VLCFAs) and their differentiation status. We investigated <jats:italic>ABCD2<\/jats:italic> and pro\u2010inflammatory gene expression, restoration of defective peroxisomal \u00df\u2010oxidation activity, accumulation of very long\u2010chain fatty acids (VLCFA) and differentiation status. Three advanced cerebral X\u2010ALD patients received Vorinostat and CSF and MRI diagnostics was carried out in one patient after 80\u00a0days of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Vorinostat improved the metabolic defects in X\u2010ALD macrophages by stimulating <jats:italic>ABCD2<\/jats:italic> expression, peroxisomal \u00df\u2010oxidation, and ameliorating VLCFA accumulation. Vorinostat interfered with pro\u2010inflammatory skewing of X\u2010ALD macrophages by correcting <jats:italic>IL12B<\/jats:italic> expression and further reducing monocyte differentiation. Vorinostat normalized the albumin and immunoglobulin CSF\u2010serum ratios, but not gadolinium enhancement upon 80\u00a0days of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The beneficial effects of HDAC inhibitors on macrophages in X\u2010ALD and the improvement of the blood\u2010CSF\/blood\u2010brain barrier are encouraging for future investigations. In contrast with Vorinostat, less toxic macrophage\u2010specific HDAC inhibitors might improve also the clinical state of X\u2010ALD patients with advanced inflammatory demyelination.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51015","type":"journal-article","created":{"date-parts":[[2020,5,2]],"date-time":"2020-05-02T09:02:00Z","timestamp":1588410120000},"page":"639-652","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Vorinostat in the acute neuroinflammatory form of X\u2010linked adrenoleukodystrophy"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5357-2630","authenticated-orcid":false,"given":"Bettina","family":"Zierfuss","sequence":"first","affiliation":[{"name":"Department of Pathobiology of the Nervous System Center for Brain Research Medical University of Vienna Vienna 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