5-aza Heart Study
Research type
Research Study
Full title
Assessing the DNA methylation inhibitory effects of 5-azacytidine on cardiac relevant genes: a pilot study
IRAS ID
253423
Contact name
Paula Tighe
Contact email
Sponsor organisation
Queen's University Belfast
Duration of Study in the UK
2 years, 11 months, 30 days
Research summary
Hypertrophic Cardiomyopathies (HCM) are a group of heart diseases characterised by enlargement of the heart (cardiac hypertrophy). Cardiac hypertrophy causes the heart muscle to stiffen, impairing its ability to pump blood efficiently, resulting in heart failure. Although HCM has a prevalence of 1 in 500 in developed countries there are no therapies that directly target the underlying disease mechanisms. DNA methylation is a novel, reversible process that can silence the expression of specific genes in disease. Our recent work has identified Macrophage Scavenger Receptor 1 (MSR1), Hes-Related Family BHLH Transcription Factor With YRPW Motif 2 (HEY2), Major facilitator superfamily domain containing 2b (MFSD2B) and Myosin binding protein C3 (MYBP-C3) as novel hypermethylated cardiac genes. This project aims to assess whether the DNA methylation inhibitor 5-azacytidine (5-aza, Vidaza) can increase circulating levels of MSR1, HEY2, MFSD2B and MYBP-C3 by reversing hypermethylation, and if these changes correlate with cardiac structure and function. 5-aza is currently used for the treatment of haematology patients with myeloid malignancies. We plan to collect data on myeloid malignancy patients attending Belfast City Hospital for 5-aza treatment as part of their usual disease management. We will collect blood and study samples before and during 5-aza treatment from patients naïve to 5-aza therapy to measure markers that reflect DNA methylation changes in genes of interest, markers that reflect changes in heart structure and function, and to explore functional properties of cardiac relevant cell types derived from the blood. We will also look for structural and functional changes in the heart using echocardiography and correlate these parameters with the circulating concentrations of the blood markers. Data from this study will help provide evidence that DNA methylation inhibitors can alter expression levels of genes associated with heart disease, supporting the need for further research into developing drug targets for these molecules.
REC name
South Central - Hampshire B Research Ethics Committee
REC reference
24/SC/0275
Date of REC Opinion
13 Sep 2024
REC opinion
Further Information Favourable Opinion