August 30, 2021 - September 1, 2021

Pharmacological targeting of cathepsin C: a key therapeutic target in chronic inflammatory and auto-immune diseases

2nd meeting

MEMBERS

Description

Cathepsin C (CatC), also known as dipeptidyl peptidase I, is a lysosomal amino peptidase belonging to the papain family of cysteine peptidases.  CatC catalyzes the cleavage of two residues from the N-termini of peptides and proteins. CatC, which is ubiquitously expressed in mammals is considered to be a major intracellular processing enzyme. The best well-known function of CatC is the activation of immune cell-associated serine proteinases such as neutrophil serine proteinases (NSPs). Neutrophil-associated local proteolysis is a common pathogenic phenomenon in chronic inflammatory or autoimmune diseases. Most extracellularly secreted proteinases occur as inactive zymogens and require activation. By contrast, NSPs elastase, proteinase 3, cathepsin G, and NSP4 are fully processed and are stored as active enzymes in granules of the regulated secretory pathway. Loss of function mutations in the CatC gene cause Papillon-Lefèvre syndrome (PLS) characterized by a severe pre-pubertal periodontitis and palmoplantar keratoderma without marked immunodeficiency. The lack of CatC activity results in an almost total elimination of NSPs in neutrophils from PLS patients. Moreover, PLS fibroblasts showed reduced growth rates and abnormal morphology with marked autophagic dysfunction. The main objective of the "Cathepsin C’s Five" consortium is to explore the pharmacological targeting of CatC in fundamental and translational research for drug development. To keep track and counterbalance unwanted effects of granule-associated serine proteinases amplified by CatC, we will evaluate new chemical inhibitors directly or indirectly targeting CatC in in vitro and in vivo experimental disease models. The proteinase-lowering drugs may be directly applicable to COPD, autoimmune vasculitis or psoriatic patients. These therapeutics may also be beneficial for patients with idiopathic pulmonary fibrosis by impairing the aberrant activation of fibroblasts.

Programme (GMT+2:00 - Paris Time)

Monday 30th August 2021:

 

  • 14:00 Opening and Welcome Speech (B. Korkmaz)
  • 14:05 HORIZON-HLTH-2021-DISEASE-04-02: Building a European innovation platform for the repurposing of medicinal products (P. Rio & F. Metzinger)
  • 14:15 Presentation of EURO-PROT (B. Korkmaz)
  • 14:45 Description of WP1: Project coordination and management  (B. Korkmaz & A. Montagu)
  • 15:00 Description of WP2: Financial, legal, ethical and social aspects of repositioning

Discussion

  • 15:20 Description of WP4: Biochemical pharmacology of drugs for repositioning (M. Novinec & A. Walls)

Task 4.2 (P. Bonnet)

Task 4.6 (G. Lalmanach)

Discussion

  • 15:45 Description of WP3: Identification of new targets for drug repositioning (M. Cordero & A. Vlahou)

Task 3.1 (B. Korkmaz)

Task 3.2 (M. Cadène)

Discussion

  • 16:00 New EURO-PROT participant: Critical Path: a catalyst in the development of new approaches to advance medical innovation and regulatory science. (C. Olivier)

 

Tuesday 31st August 2021

 

  • 14:00 Description of WP5: Molecular imaging of the efficacy of drugs for repositioning (A. Lesner & P. Mellet)

Tasks 5.1-5.2-5.3 (M. Sienczyk)

Task 5.4 (S. Marque)

  • 14:20 Description of WP6: Repositioning ofdrugs in acute inflammation (A. Aghdassi & N. Meunier)

Task 6.4 (R. Kettritz)

Task 6.5 (S. Korkmaz) preliminary data

  • 14:40 Description of WP7: Repositioning ofdrugs in chronic inflammation (J. Chichy & M. Rhimi)

Task 7.1 (I. Couillin) preliminary data

  • 15:00 Description of WP8: Repositioning ofdrugs in cancer (F. Yagci-Acar & C. Beauvillain)

Task 8.1 (I. Koç & N. Mignet)

Task 8.2 (E. Ulukaya)

  • 15:30 New EURO-PROT participant: European Research Infrastructure EU-OPENSCREEN (W. Fecke)

 

Wednesday 1st September 2021

 

  • 14:00  EURO-PROT impact (B. Korkmaz)

Discussion

  • 14:30  Description of WP9: Clinical research & Clinical trials withdrugs for repositioning (R. Kettritz)

 

Task 9.2 (R. Stockley)

Discussion

  • 15:00 : Description of WP10: Joint activities and Communication & Dissemination & Exploitation (R. Vanbever & S. Korkmaz)

Tasks 10.1-10.3 (D. Scherman) 

Discussion

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