A biobank approach for frontotemporal dementia and Parkinson’s drug development
Frontotemporal dementia (FTD) and Parkinson’s disease (PD) are devastating neurodegenerative disorders that impact the patient’s quality of life. These diseases are clinically, genetically, and pathologically heterogeneous, hampering targeted drug development. In the CONCERT project, we collaborated closely with principal investigators of F.Hoffmann La Roche Ltd. Together to identify validate the druggable targets for thereapeutic strategies and skin biomarkers for FTD and PD.
The biobank and large molecular datasets of FTD and PD patients can stimulate cellular and translational research and drug discovery for neurodegenerative disease and have, as such, great economic value (> 1.000.000 EURO). Identified druggable targets can aid in the development of disease-modifying treatment of FTD and PD. Knowledge of the molecular profiles and (common) disease mechanisms involved in protein aggregation in FTD and PD will aid the development of biomarkers for early diagnosis of neurodegenerative disorders.
In this CONCERT project, we used a unique integrated within-subject approach to unravel molecular profiles and identify targets for disease-modifying treatment strategies for FTD and PD. We included postmortem brain tissue and skin biopsies 43 FTD and 26 PD Cases between 2020 and 2024. Additional postmortem brain tissue was selected and obtained from the brainbank for biochemical analysis. Morphological, pathological and biochemical data were collected of the tissue samples and compared with datasets of individuals with other neurodegenerative disorders, including Alzheimer’s disease.
In summary, we have setup a biobank including fibroblasts, iPSC lines and postmortem brain tissue samples of wellcharacterized pathologically-confirmed FTD and PD patients to stimulate translational research and the identification of druggable targets.
We have generated a very large set of proteome data of brain tissue of FTD, sPD and controls (incl AD and nonneurologic controls) which can be mined to identify disease-specific targets and biomarkers. We have identified molecular subtypes in FTD and PD, which we plan to validate in followup studies. We have provided proof of concept that aSyn skin levels hold potential as diagnostic biomarker for PD/DLB. Further optimization of the immunoassay for clinical skin samples is ongoing.
