Relevance of Biochemical Deep Phenotyping for a Personalised Approach to Parkinson's Disease. (10th February 2023) - Giuliano, Claudio
Highlights: Stratification studies for Parkinson's disease are at early stage. Extracellular vesicles have attracted attention for PD biomarker discovery. Patient subgroups subdivision could allow a tailored disease-modifying therapies. The deep phenotyping concept has emerged recently in the PD field. The deep phenotyping approach may draw a unique multi-dimensional patient profile. Abstract: Parkinson's disease (PD) is a multifactorial neurodegenerative disorder characterised by the progressive loss of dopaminergic neurons in the nigrostriatal tract. The identification of disease-modifying therapies is the Holy Grail of PD research, but to date no drug has been approved as such a therapy. A possible reason is the remarkable phenotypic heterogeneity of PD patients, which can generate confusion in the interpretation of results or even mask the efficacy of a therapeutic intervention. This heterogeneity should be taken into account in clinical trials, stratifying patients by their expected response to drugs designed to engage selected molecular targets. In this setting, stratification methods (clinical and genetic) should be supported by biochemical phenotyping of PD patients, in line with the deep phenotyping concept. Collection, from single patients, of a range of biological samples would streamline the generation of these profiles. Several studies have proposed biochemical characterisations of patient cohorts based on analysis of blood, cerebrospinal fluid, urine, stool, saliva and skin biopsy samples, with extracellular vesicles attracting increasing interest as a source of biomarkers. In this review we report and critically discuss major studies that used a biochemical approach to stratify their PD cohorts. The analyte most studied is α-synuclein, while other studies have focused on neurofilament light chain, lysosomal proteins, inflammasome-related proteins, LRRK2 and the urinary proteome. At present, stratification of PD patients, while promising, is still a nascent approach. Deep phenotyping of patients will allow clinical researchers to identify homogeneous subgroups for the investigation of tailored disease-modifying therapies, enhancing the chances of therapeutic success.