Project: Defining stratification of patients with C3 Glomerulopathies /Immune complex –mediated glomerular diseases for better diagnosis and tailored treatment

Acronym	DECODE (Reference Number: ERAPERMED2020-151)
Project Topic	Primary membranoproliferative glomerulonephritis (MPGN) represents a group of rare kidney disorders classified into alternative pathway complement-mediated C3 glomerulopathy (C3G) and immune-complex-mediated MPGN (IC-MPGN). However alternative pathway abnormalities are observed in IC-MPGN as frequently as in C3G. There is no effective therapy. Several compounds that target different complement molecules are in clinical development and may be therapeutic options for C3G/IC-MPGN. However, C3G/IC-MPGN are heterogenous diseases and different patients have abnormal activation at different levels of the complement cascade. This necessitates a pathogenesis-driven re-classification. Recently, through a data-driven statistical approach, we identified 4 clusters of C3G/IC-MPGN patients characterized by different pathogenetic patterns and clinical features. In this project we will combine omics approaches (i.e. WES, proteomics and metabolomics) and hierarchical clustering analysis to define a precise stratification of patients with primary C3G/IC-MPGN, and to identify specific biomarkers, which will be instrumental for diagnosis, predicting prognosis and tailoring the right therapeutic strategy for the right patients, towards personalized medicine. The specific aims are:1) To obtain patient stratification in a large cohort of patients who will be characterized in depth genetically and immunologically. 2) To identify specific biomarkers in each cluster by investigating the proteomics and metabolomics profiles in plasma and urine. 3) To evaluate in each cluster the effects of complement inhibitors or other compounds in pre-clinical ex-vivo studies. 4) To design cluster-tailored treatment protocols. 5) To address ethical, legal and social aspects. The results of DECODE will be essential for the success of clinical trials and will offer patients a greater chance of recovery, limit the side effects of unselective drugs, and reduce costs.
Network	ERA PerMed
Call	3rd Joint Transnational Call for Proposals (2020)

Project partner

Number	Name	Role	Country
1	Istituto di Ricerche Farmacologiche Mario Negri IRCCS	Coordinator	Italy
2	ASST-Papa Giovanni XXIII	Partner	Italy
3	Biomedical Research Foundation Academy	Partner	Greece
4	Helmholtz Zentrum Munchen	Partner	Germany
5	Norwegian Institute of Public Health	Partner	Norway
6	University of Leipzig	Partner	Germany