Dataset Information

Full blood mRNA sequencing of myotonic dystrophy type 1 patients after cognitive behavioural therapy

ABSTRACT: Myotonic dystrophy type 1 (DM1) is an incurable multisystem disease caused by a CTG-repeat expansion in the DM1 protein kinase (DMPK) gene. The OPTIMISTIC clinical trial demonstrated positive and heterogenous effects of cognitive behavioral therapy (CBT) on the capacity for activity and social participations in DM1 patients. Here, we performed mRNA sequencing of full blood for 27 patients of the OPTIMISTIC cohort before and after the CBT intervention. We identified 608 genes for which their expression was significantly associated with the disease causing CTG-repeat expansion, as well as with 1176 genes significantly associated with the average clinical response towards the intervention. Remarkably, all 97 genes significantly associated with both returned to more normal levels in patients who benefited most from CBT. This trend was consistent with the difference observed between DM1 patients and controls in an earlier study of blood mRNA expression levels, singling these genes out as candidate biomarkers for therapy response. Together these results highlight the ability to find disease relevant information in full blood of DM1 patients and open new avenues to monitor therapy effects.

PROVIDER: EGAS00001005830 | EGA |

REPOSITORIES: EGA

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Publications

Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1: a multicentre, single-blind, randomised trial.

Okkersen Kees K Jimenez-Moreno Cecilia C Wenninger Stephan S Daidj Ferroudja F Glennon Jeffrey J Cumming Sarah S Littleford Roberta R Monckton Darren G DG Lochmüller Hanns H Catt Michael M Faber Catharina G CG Hapca Adrian A Donnan Peter T PT Gorman Gráinne G Bassez Guillaume G Schoser Benedikt B Knoop Hans H Treweek Shaun S van Engelen Baziel G M BGM

The Lancet. Neurology 20180619 8

<h4>Background</h4>Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care alone improved the health status of patients with myotonic dystrophy type 1.<h4>Methods</h4>We did a multicentre, single-blind, randomised trial, ...[more]

PMID: 29934199

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Project description:The purpose of this study was (1) to identify novel genes involved in the pathogenesis of Rheumatoid Arthritis (RA) disease, which may provide additional targets for therapeutic intervention and (2) to examine the molecular mechanisms associated with the response to anti-TNF treatment. Microarray analysis of LPS-stimulated whole blood from RA patients pre and post anti-TNF treatment was conducted. This study identified 818 transcripts, differentially expressed in RA patients pre-treatment compared to non-RA control samples. While a number of these genes were associated with RA in previous studies, validating our data, a number of novel genes with possible functions in RA disease were also identified. The number of transcripts (1051) significantly altered post anti-TNF treatment indicates the impact of anti-TNF therapy on systemic gene expression. A number of these transcripts were confirmed to be altered in a larger patient group and may represent potential genetic markers of a patientâs clinical response to anti-TNF treatment. Experiment Overall Design: Transcriptome profiling was performed on two RA patients, pre- and three months post-Enbrel therapy and two matched non-RA controls. The whole blood model described by Wang et al (2000) was used with minor modifications. Briefly, to EDTA anti-coagulated blood, LPS (30ng/ml) was added immediately after drawing, and incubated at 37oC for 4 hours, mixing at 80s. After 4 hours red blood cells were lysed and pelleted, white cells were washed once in PBS (Gibco) and frozen at â70oC for subsequent RNA extraction. Total RNA was extracted using the RNeasy kit (QIAGEN) as per manufacturerâs instructions. Samples were treated with DNA-Free (Ambion) to remove genomic DNA and checked using intron-overlapping primers prior to generating cRNA probes or cDNA (data not shown). Affymetrix array data was normalised (globally) and statistically (t-test) analysed using GeneSight software (Biodiscovery). Gene expression changes with a p value of < 0.05 and a fold change of 3 or greater were considered differentially expressed.

Dataset Information

Full blood mRNA sequencing of myotonic dystrophy type 1 patients after cognitive behavioural therapy

Publications

Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1: a multicentre, single-blind, randomised trial.

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