Vorinostat in the acute neuroinflammatory form of X-linked adrenoleukodystrophy.

ABSTRACT:

Objective

To 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.

Methods

A 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 inv

SUBMITTER: Zierfuss B 

PROVIDER: S-EPMC7261758 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature