Patient-induced pluripotent stem cells for multi-omic network-based stratification of synucleinopathies to deliver personalized treatments

Neurodegenerative diseases (NDDs) are complex multifactorial diseases that may initiate during development or at early adulthood, and progress during ageing and/or when exposed to environmental stressors. At the time of diagnosis, the brain has “passed the point of no return” to be cured.

Gaining knowledge on early disease mechanisms will allow the rational development of tailored treatments that can prevent or delay disease onset and progression.

The overarching goal of the project is to decipher the origin of synucleinopathies Parkinson’s disease (PD) and multiple system atrophy (MSA), by revealing dysfunctional networks and pathways that lead to neuronal cell-type specific injury. PD segregates into familial and idiopathic cases, whereas MSA has an idiopathic origin.

Based on our recent findings, we hypothesize that well-defined familial forms of PD can be used as initial templates to study cellular dysfunctions in idiopathic PD and MSA, and to examine the specificity of the pathways that dictate PD and MSA pathogenicity, when compared to other NDDs.

This will be explored by performing a multi-omic (transcriptomics, proteomics and metabolomics) network-based analysis using patient brain cell types generated from induced pluripotent stem cells.

Our investigations will be complemented by analysing dysfunctional networks and pathways at end stage of disease using post-mortem tissue. The project will provide knowledge to develop tailored treatments.