Prodromal DEtErminants for PhENoconversion of idiopathic RBD to alpha-synucleinopathies (PD, DLB and MSA) [DEEPEN-iRBD]
Progetto Problem:
Evidence shows that individuals affected by idiopathic REM sleep behavior disorder (iRBD) have a high risk of conversion to Parkinson’s disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA), conditions that have a common cellular pathological hallmark, the aggregation of alpha-synuclein (aSYN). Despite phenotypic similarities in the early stages, clinical phenotypes differ significantly in later stages with substantial therapeutic and prognostic consequences.
Aim and methods:
DEEPEN-iRBD aims to develop a proof of concept for prediction of phenoconversion based on pre-clinical/clinical research and data analysis to implement i) correct early diagnosis, ii) accurate individual prognosis, iii) facilitate personalized therapeutic interventions. We will integrate existing and new data, including both advanced clinical assessments and molecular markers to deepen iRBD and reveal PD, MSA and DLB specific profiling at the prodromal stage. Clinical signals (polysomnography, electrocardiogram and arterial blood pressure) will determine autonomic functions. A comprehensive genetic screening will identify inherited disease modifiers. Patient samples as body fluids, skin biopsy, and iPSC-derived brain cells will be employed to determine structure and properties of aSYN aggregates and disease-specific cellular pathways. Pathogenicity model, a system for prediction and description of diseases, will be applied for individual diagnosis and patient stratification. On this basis, a personalized therapeutical approach combined with early preventive intervention could be tailored to individuals with iRBD. Finally, ethical and social aspects related to communication and screening of people at risk in a prodromal stage will be evaluated.
Benefit:
The multidisciplinary consortium will deep aspects of secondary and tertiary prevention, mainly through individual risk assessment and strategies to develop tailored interventions and care for iRBD individuals.