Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Epigenetic Research bridges Clinical Research Gaps in Schizophrenia: Epigenetic Biomarker Development and Informed Consent Process Considerations in Clinical Trials

Martina Kirsch (Abschlußjahr: 2016)

Summary
Language: English
Epigenetics reaches back into the 1940s when this field of research was first characterized by the British developmental biologist Conrad Hal Waddington (8 November 1905 – 26 September 1975) as the interaction between an organism’s, individual’s, or cell’s genes and its environment which can influence gene expression and lead to different phenotypes. Whereas genetic mutations are irreversible, epigenetic changes are reversible and can be influenced by pharmacological treatment. Therefore, epigenetics provides a new perspective in the treatment of high complex psychiatric disorders like schizophrenia.
Schizophrenia is a severely debilitating, heterogeneous disorder characterized by an array of clinical manifestations related to metabolic or hormonal dysregulation occurring in up to 1% of the world’s population. A low response rate of less than 50% to initial treatment with antipsychotic medication, the number and severity of occurring adverse events, lack of social support, and the relapse itself can lead to patient’s suicide.  
This master thesis aims to demonstrate that the predictive epigenetic biomarker Valproate (a histone deacetylase inhibitor), which is also an antipsychotic medicament, can bridge the conventional treatment of schizophrenia by supporting physicians in early intervention by identifying subjects who are most likely to benefit from its treatment in the psychotic phase of schizophrenia.
Generally, any genetic testing can reveal further comorbidities or predispositions for another, in worst case severe disease in addition to the initial one being the reason for testing. Therefore, specific considerations in the informed consent process are to be followed to ensure patient safety, integrity and data protection at any time. As example, selected core elements of an informed consent form for adults in schizophrenia will be described under consideration of the respective laws in clinical studies being conducted in Europe and USA.
At the end of this thesis, the translation of a predictive epigenetic biomarker into clinical routine practice will be addressed to outline the considerations to be taken for its implementation in the treatment of schizophrenia. Future prospect of epigenetic biomarker application in schizophrenia means that it may contribute to a more efficacious treatment to maintain patient compliance and to reduce relapse rates at the different stages of schizophrenia disease. Further research of the different epigenetic mechanisms in post-mortem brains and peripheral blood mononuclear cells of schizophrenic patients will very probably promote development of new innovative drugs allowing targeted treatment of the applicable epigenetic aberration in schizophrenic patients.
Pages: 67