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Histone deacetylase inhibitors reverse gene silencing in Friedreich's ataxia
A class of histone deacetylase (HDAC) inhibitors that reverse FXN silencing in primary lymphocytes from individuals with Friedreich's ataxia are described and it is shown that these molecules directly affect the histones associated with FXN, increasing acetylation at particular lysine residues on histones H3 and H4. Expand
The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional abnormalities in Huntington's disease transgenic mice
Chronic oral administration of HDACi 4b, beginning after the onset of motor deficits, significantly improved motor performance, overall appearance, and body weight of symptomatic R6/2300Q transgenic mice, and may offer clinical benefit for HD patients and provide a novel set of potential biomarkers for clinical assessment. Expand
HDAC Inhibitors Correct Frataxin Deficiency in a Friedreich Ataxia Mouse Model
Lack of acute toxicity, normalization of frataxin levels and of the transcription profile changes resulting from fratxin deficiency provide strong support to a possible efficacy of this or related compounds in reverting the pathological process in Friedreich ataxia, a so far incurable neurodegenerative disease. Expand
Friedreich's ataxia induced pluripotent stem cells model intergenerational GAA⋅TTC triplet repeat instability.
The derivation of induced pluripotent stem cells (iPSCs) from FRDA patient fibroblasts by transcription factor reprogramming is reported, and shRNA silencing of MSH2 impedes repeat expansion, providing a possible molecular explanation for repeat expansion in FRDA. Expand
Role of Mismatch Repair Enzymes in GAA·TTC Triplet-repeat Expansion in Friedreich Ataxia Induced Pluripotent Stem Cells*
Background: Friedreich ataxia is caused by a GAA·TTC triplet-repeat expansion in the first intron of the FXN gene. Results: Expansion of the repeats is observed in induced pluripotent stem cellsExpand
RNA Toxicity and Missplicing in the Common Eye Disease Fuchs Endothelial Corneal Dystrophy*
The first instance of RNA toxicity and missplicing in a common non-neurological/neuromuscular disease associated with a repeat expansion is reported. Expand
Two New Pimelic Diphenylamide HDAC Inhibitors Induce Sustained Frataxin Upregulation in Cells from Friedreich's Ataxia Patients and in a Mouse Model
The results support the pre-clinical development of a therapeutic approach based on pimelic diphenylamide HDACIs for FRDA and provide information for the design of future human trials of these drugs, suggesting an intermittent administration of the drug. Expand
Rationale for the Development of 2-Aminobenzamide Histone Deacetylase Inhibitors as Therapeutics for Friedreich Ataxia
Studies with model compounds show that these histone deacetylase inhibitors increase FXN messenger RNA levels in the brain in mouse models for Friedreich ataxia and relieve neurological symptoms observed in mice models and support the notion that this class of molecules may serve as therapeutics for the human disease. Expand
Epigenetic therapy for Friedreich ataxia
To investigate whether a histone deacetylase inhibitor (HDACi) would be effective in an in vitro model for the neurodegenerative disease Friedreich ataxia (FRDA) and to evaluate safety and surrogateExpand
Length-dependent CTG·CAG triplet-repeat expansion in myotonic dystrophy patient-derived induced pluripotent stem cells.
Myotonic dystrophy type 1 (DM1) is an inherited dominant muscular dystrophy caused by expanded CTG·CAG triplet repeats in the 3' untranslated region of the DMPK1 gene, which produces a toxicExpand