The overall objective of the WP5 project is to develop and test novel biological therapeutic approaches of inflammatory diseases, based on the accumulated knowledge provided by WP1 to 4 and focusing on a better understanding of the molecular mechanisms involved in both disease initiation and progression. This involves the clinical and fundamental expertise of the consortium members in inflammatory diseases affecting various organs or physiological systems (kidney, lung, gut, liver, pancreas, hematopoietic system and joints). These diseases are a major cause of morbidity and mortality and both personal factors (e.g., genetic predisposition, associated diseases) and environmental features play an instrumental role in their pathogenesis. Although these diseases display different etiologies and clinical characteristics, they share a number of molecular patterns and physiopathologic features, including an exaggerated inflammatory and immune or auto-immune response and morphologic alterations known under the term of ’tissue remodeling’, that reflect an abnormal repair process to acute or chronic insults. This remodeling response results in tissue fibrosis that remains the major cause of organ failure and benefits so far to limited treatment options. Although advances have been made, therapy of these diseases is still mostly symptomatic, and based essentially on corticosteroids or immunosuppressive drugs. In addition, subgroups of patients respond poorly even to systemic administration of high-dose of corticosteroids and novel bio-therapies that emerged during the last few years improved only part of them, or even failed. Strikingly, these subgroups account for approximately most of total health care costs and, therefore, the elucidation of the pathways initiating and/or aggravating these diseases and for a better patient stratification is crucial for the identification of novel therapeutic tools.
The Teams involved in WP5 developed, or actively participate in several large national and European prospective cohorts aimed at sharing clinical data and biological samples (DNA, serum/plasma, urine, and cell/tissue samples). Studies are conducted to decipher the genetic and molecular signatures of these inflammatory diseases in affected organs and in relevant cell types, using original technologies, including SNP sequencing, cytogenetics, bio-imaging, proteomics, Multiplex- and computation-based approaches.
The main foreseeable consequences of the research program of WP5 are:
(i) a better understanding of the mechanisms involved in the onset and progression of these diseases
(ii) the discovery of novel markers for patient screening, follow-up and response to treatment, of new risk factors for disease onset and progression and, ultimately,
(iii) the identification of new therapeutic targets.