DIAGNOSIS aims to develop novel diagnostic biomarker signatures with high specificity at early stages of the disease. The first candidate biomarker signature of the DIAGNOSIS project will be derived from an already established, state-of-the-art PD cohort (DeNoPa study from the Paracelsus-Elena Clinic in Kassel, Germany led by Prof. Dr. Brit Mollenhauer that includes newly diagnosed, drug-naive PD patients.
During the project, molecular data derived of DeNoPa subjects will comprise proteomic, transcriptomic, and metabolomic data from blood samples. The omics data will be combined with clinical data and used as the input for pathway and network analyses as well as for mechanism-based computational models of the metabolic system. This strategy will allow the data to be interpreted on the network level to identify robust biomarker signatures. The mechanistic understanding of PD will provide a basis for the development of a new diagnosis of PD and a starting point for investigating intervention possibilities.
The DIAGNOSIS project will then test whether the diagnostic biomarker signatures for motor-phase PD can also be used, either in full or in part, for the diagnosis of prodromal PD. For this evaluation, samples and data will be analyzed from a longitudinal study of subjects at risk for neurodegenerative disorders (TREND study from the University of Tübingen, Germany led by Prof. Dr. Daniela Berg).
The subjects recruited for TREND have prodromal non-motor symptoms at baseline and are being followed over the years and any conversion to a neurodegenerative disease is monitored. These patients diagnosed with PD can be tracked back to the time before this conversion. An unbiased, comparative analysis of omics data time points before and after conversion to PD will be used to derive biomarker signatures that predict the disease with high likelihood before the onset of clinically diagnostic features. As a long-term goal, the mechanistic interpretation of the validated biomarker signatures will be a starting point from which to study preventive approaches that delay or prevent the onset of the disease.