Developing minimally invasive, high throughput, low cost molecular assays for the early diagnosis of schizophrenia and other psychiatric disorders.
Project aim and objective
The current diagnosis of schizophrenia involves examination and monitoring by psychiatrists, a process which can take between 2 and 5 years. Currently, schizophrenia is diagnosed on the basis of patient reports and several clinical observations. By any reckoning this is a rather subjective and sometimes long-lasting uncertain process.
The SchizDX application proposed to identify and validate up to 50 biomarkers relevant to the first onset of schizophrenia. In this project, label-free nano-LC-MS based proteomic rofiling, in combination with glycoprotein profiling and existing analyte assay screening, was utilised to establish a schizophrenia-specific disease biomarker pattern/signature etectable in blood.
A critical phase of the project was the collection of high quality clinical samples to support the biomarker development efforts and 800 samples were collected for the main validation study and to identify up to 50 candidate biomarkers which showed changes in concentration in drug naive, first onset schizophrenia patient cerebrospinal fluid and serum samples or changing in similar patients following 4 weeks of antipsychotic drug treatment.
Over the course of this project, several potential molecular biomarkers were identified by Psynova Neurotech Ltd. Other candidate biomarkers were selected based on findings in the literature. The main aim was to produce new immunoassays for incorporation into new multiplex tests for schizophrenia. Thirteen of these assays have already been incorporated into the Myriad-RBM DiscoveryMAP immunoassay platform which has been used for profiling in the large scale validation study. In addition, 9 further assays have been developed as extra contributions for incorporation into future multiplex immunoassays for the study of psychiatric disorders and their treatment.
A novel ex vivo blood culture system (TruCulture) combined with the use of a 33-plex cytokine/chemokine immunoassay panel was implemented to identify further schizophrenia biomarkers and to provide a clinically-relevant system for identification of drug-predictive or response biomarkers and for novel drug discovery.
The task to carry out validation of 800 samples using the novel schizophrenia biomarker panels proved to be a ground-breaking development of a serum-based test to help confirm the diagnosis of schizophrenia. A multiplex panel of 51 immunoassays was developed that allowed reproducible identification of schizophrenia patients compared to controls with high sensitivity and specificity.
The project has resulted in a number of novel discoveries which has resulted in the application for 9 patents to establish a priority date.
Perhaps of most importance, the SchizDX project has resulted in the launch of the first molecular assay for the diagnosis of schizophrenia (VeriPsych®) by Psynova and Myriad-RBM in the USA. The test is being marketed to assist with the diagnosis of first onset schizophrenia and may result in a quicker and more cost effective diagnosis for some patients. It is well known that early intervention can result in a much better outcome for schizophrenia patients. Therefore, the outputs from the SchizDX project may be of significant benefit to patients and their families.
The suite of biomarkers identified by the project is also being evaluated for diagnosis of other mental disorders including bipolar disorder, various forms of depression and autism etc. It is often challenging for clinicians to distinguish between these disorders due to overlapping symptoms so a molecular test capable of differentiating between disorders would be of major benefit to patients.
The societal benefit of improved diagnosis of mental disorders will be manifested through more effective treatment of patients leading to a reduced financial burden on healthcare systems and better integration of patients into the community.
The SchizDX project is contributing to a better understanding of mental disorders such as schizophrenia and, in time, this improved understanding may help to combat the widespread negative attitudes towards the mentally ill.
Psynova Neurotech Ltd, UK
Cambridge University, UK
Central Institute of Mental Health, Germany
University of Muenster, Germany
EDI GmbH, Germany
Pera Innovation, UK
The National Institute for Bioprocessing Research and Training, Ireland
Rules Based Medicine Inc., USA
Seventh Framework Programme (Health): Small or medium-scale focused research projects (FP7 HEALTH – 2007 – 1.1-4 223427)