Towards Personalised Brain Therapies
A molecular understanding of underlying disease processes is a fundamental prerequisite if pre-symptomatic diagnostics and high value therapeutics are to be developed. The use of global molecular profiling techniques on diseased brains can help to elucidate fundamental disease mechanisms, reveal disease sub-types, and identify novel drug targets. However, if biomarkers can also be found in readily accessible body fluids, such as cerebrospinal fluid, serum, urine or saliva, and measured over time, they open up the possibility of predicting and monitoring treatment response and compliance, aiding patient stratification and developing new early or pre-symptomatic treatments to improve outcomes or even prevent pathology. With current subjective diagnosis methods early intervention is rare; however, on those occasions it has been applied, substantial reductions in the number of inpatient days and the time to remission were achieved. Therefore, a readily-available objective test providing earlier and more accurate diagnosis of the disease would deliver not only improved patient outcomes but would also reduce the overall cost of schizophrenia to the healthcare services and society, in general.
The validation of biomarkers that can detect early changes specifically correlated to reversal or progression of mental disorders is crucial for intervention. Used as predictors, these biomarkers can help to identify high risk individuals and disease sub-groups who could serve as target populations for chemo-intervention trials, whilst as surrogate endpoints, biomarkers have the potential for assessing the efficacy and cost effectiveness of preventative interventions at a speed which is not possible when the incidence of manifest mental disorder is used as the endpoint. These biomarkers are also of use in the preclinical setting for both the development and validation of preclinical disease models.
We have established proof of principle for our approach, having already identified biomarkers in patient serum and cerebrospinal fluid as well as disease gene signatures in human brain. Once putative biomarkers in accessible fluids have been identified, polyclonal or monoclonal antibodies can be raised against them and exploited in developing immunoassays or sensor technologies.