New biomarkers for predicting antipsychotic treatment response in a patient with schizophrenia

A fundamental shortcoming in the current treatment of schizophrenia is the lack of valid criteria to predict who will respond to antipsychotic treatment. The identification of blood-based biological markers of the therapeutic response would enable clinicians to identify the subgroup of patients in whom conventional antipsychotic treatment is ineffective and offer alternative treatments. As part of the Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE) programme, the inventors conducted a transcriptome analysis on 188 subjects with first episode psychosis, all of whom were subsequently treated with amisulpride for 4 weeks. They identify 32 genes for which the expression changed after treatment in good responders only. Among these genes, the expression of ALPL, a gene involved in vitamin B6 metabolism, as well as CA4, DHRS13, and HOMER3 predicted response status before treatment. Using genotypic variations associated with expression changes, the inventors built a response eQTL-based polygenic score that predicted poor response to medication. Thus, the present invention relates to a method for predicting the response to antipsychotic drugs comprising determining the expression of the ALPL, CA4, DHRS13, or HOMER3 and/or an eQTL-based polygenic score.

Keywords: RNA-Seq, RT-PCR, Transcriptomics, Treatment Response in Schizophrenia, Schizophreniform disorder, Schizoaffective disorder, Psychosis
Patent Application number: EP19 305 528.2

Reference:

BIO19073-D1

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Pierre MAZOT
Pierre MAZOT
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Patent filling date: 2019-04-24

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