Project EDDA-R – Characterization of novel epigenetic biomarkers of alcohol dependence, therapy outcome and the risk of…

Basic data

Acronym:
EDDA-R
Title:
Characterization of novel epigenetic biomarkers of alcohol dependence, therapy outcome and the risk of relapse
Duration:
01/01/2020 to 31/12/2023
Abstract / short description:
Alcohol dependence (AD) is a severe disorder which contributes substantially to the global burden of disease. However, despite the deleterious effects of alcohol, optimal therapeutic and preventive strategies for AD are lacking, which is especially apparent as the number of patients relapsing after initially successful treatment is very high (up to 75%).
The aetiology of AD is influenced by genetic (heritability estimates: 40 – 60%) as well as environmental factors and by an interplay of both. An important molecular mechanism for those G x E interactions is the epigenetic regulation of gene expression. While the contribution of alterations in DNA methylation patterns and of histone modifications in AD is widely established, a validated panel of clinically usable epigenetic biomarkers for chronic AD, treatment success and relapse risk is still missing to date. However, in order to be able to develop better treatment strategies to facilitate long-term abstinence and to prevent relapse, the establishment of such a set of epigenetic biomarkers is mandatory. Also missing is a multi-omics integration of the different layers of epigenetic information. This is necessary as epigenetic modifications do not act in isolation, but interact with each other as well as with underlying genetic factors.
The aims of this research proposal are therefore to further investigate the potential of a panel of epigenetic modifications for AD previously identified by our group, as biomarkers for disease severity, treatment success and risk of relapse after initial successful abstinence in a large cohort of AD patients and well matched healthy control individuals. We intend to extent our previous studies on HECW2, SRPK3 and GDAP1 by investigating DNA methylation of those genes in additional tissues (saliva, postmortem brain), by comparing DNA methylation pattern between brain and blood in a rat model of AD to answer the question whether peripheral DNA methylation reflects the situation in the brain, and by including other layers of epigenetic (histone modifications, miRNA effects) as well as genetic information. Furthermore, the effects of those epigenetic modifications on gene expression levels will be studied in peripheral blood (human, rat) and brain (rat) as well as by performing functional in vitro assays.
The research project will contribute to a better understanding of the biological mechanisms underlying AD, treatment response and relapse risk. Furthermore, the establishment of a set of epigenetic biomarkers of potential clinical value could prove to be useful in order to be able to develop strategies to facilitate more personalized treatment options to foster long-term abstinence and to prevent relapse. This would be highly valuable for the individual patient because for patients that are most likely not benefiting from the therapy, other treatment options could be considered early and patients at an increased risk to suffer from relapse could be monitored more closely to avoid repeated cycles of withdrawal and relapse. Moreover, it would also help to decrease treatment cost as no resources would be dissipated for non-effective treatment options and costly cycles of therapy and relapse could be prevented.

Involved staff

Managers

Department of Psychiatry and Psychotherapy
Hospitals and clinical institutes, Faculty of Medicine

Local organizational units

Department of Neurology with Focus on Epileptology
Department of Psychiatry and Psychotherapy
Hospitals and clinical institutes, Faculty of Medicine

Funders

Bonn, Nordrhein-Westfalen, Germany
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