Defining stratification of patients with C3 Glomerulopathies/immune complex-mediated glomerular diseases for better diagnosis and tailored treatment.

In this project FRRB finances the Coordinator: Istituto di Ricerche Farmacologiche Mario Negri IRCCS. The Principal Investigator responsible of the project is Dr. Ariela Benigni.

FRRB also finances partner number 1: ASST-Papa Giovanni XXIIIThe Principal Investigator is Dr. Piero Ruggenenti.

Pathology of interest:  C3 Glomerulopathies/immune complex-mediated glomerular diseases
Area of research:  Nephrology
Start date:  1st March 2021
End date:  28th February 2024
Funding:  € 492.120,00
Project partners:   - Istituto di Ricerche Farmacologiche Mario Negri IRCCS 
  - ASST-Papa Giovanni XXIII
  - Biomedical Research Foundation Academy
  - Helmholtz Zentrum München
  - Norwegian Institute of Public Health
  - University of Leipzig, Germany (ULEI)


Primary membranoproliferative glomerulonephritis represents a heterogenous group of rare kidney disorders classified  into alternative pathway complement-mediated C3 glomerulopathy (C3G) and immune-complex-mediated MPGN (IC-MPGN).

These diseases are untreatable at the moment despite a plethora of complement inhibitors developed by many companies boosted by the success of the C5 inhibitor eculizumab that was literally transformative of the natural history of patients with atypical HUS.

In the hope that the same could apply to patients with MPGN the main goal of DECODE is to improve the diagnosis and management of these very patients through precise stratification and tailored treatment protocols.

Previous studies by the Coordinator have been capable of  identifying four patient clusters, instrumental to define early and late complement activation. Building on this previous experience, here we will implement this strategy by combining omics approaches (i.e. WES, proteomics and metabolomics) and hierarchical clustering analysis to define a precise stratification of patients with 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.

This proposal will offer also the unique opportunity to study a larger cohort of patients that will be in depth characterized for genetic and immune abnormalities in the various complement components, and for their clinical and biochemical characteristics.

Specific objectives are:

  - stratify  patients  into  clusters  and  provide  easy  to  handle  platform  to assign  patients  to  each  them;
  - identify  novel  biomarkers  of  each  cluster;
  - identify  cluster specific therapies,
  - design phase 2 clinical protocols.

 DECODE will involve end users and engage with regulator and decision makers to ensure maximum exploitation and impact, taking into account ethical,legal and social implications.