- Dr. Brice Korkmaz
- Chair of International Cathepsin-C Consortium (ICat-CC), INSERM UMR-1100, Centre d’Etude des Pathologies Respiratoires, Université de Tours, Tours, France.
Website | E-mail
Special Issue Introduction
International Cathepsin-C Consortium (ICat-CC) was set up in 2016. Thanks to the participation of the world-leading specialists from academic labs and industry working on cathepsin C (CatC) and its target proteases, including neutrophil serine proteases (NSPs). Inflammation-mediated immune cell alterations are associated with many diseases, including acute, chronic inflammatory diseases and cancer. Current therapies of inflammatory diseases fail to fully control inflammatory processes in patients. There is an unmet need for new therapies that go beyond symptomatic relief and delay the progression of disease transiently. NSPs are locally released in response to pathogens and many other non-infectious danger signals. Uncontrolled NSPs are involved in neutrophil-mediated inflammatory diseases and are considered important therapeutic targets.
CatC, also called dipeptidyl peptidase 1, attracts more and more attention from both scientists and clinicians because of its role in the activation of pro-inflammatory NSPs implicated in certain chronic inflammatory/auto-immune disorders. Promising preclinical and clinical data suggest that pharmacological inhibition of NSPs might ameliorate these conditions. Patients with Papillon-Lefèvre syndrome have a genetically determined deficiency in CatC but, reassuringly, do not exhibit marked immunodeficiency despite the absence of NSPs in immune defense cells. Hence, the pharmacological control of CatC activity in bone marrow precursor cells represents an attractive therapeutic strategy for neutrophil serine protease-mediated disorders. A variety of CatC inhibitors, developed by pharmaceutical companies and academic investigators, are currently being employed and evaluated in preclinical/clinical trials as anti-inflammatory drugs. A review of the therapeutic targeting of CatC resulted from the first International Symposium on Cathepsin C IsyCatC (Tours/France, April 2017) and was published in the journal Pharmacology and Therapeutics. A CatC inhibitor is currently being tested in Phase 3 in patients with bronchiectasis, a chronic inflammatory disease defined by permanent dilatation of the bronchi. That news is very encouraging for biochemists studying the functionality of CatC, cell biologists studying its maturation and tissue localization, chemists developing specific CatC inhibitors, and clinicians managing patients with NSPs-mediated disorders. Due to overlapping phenotypes and similar underpinning molecular mechanisms for a number of diseases associated with inflammation, a positive effect in bronchiectasis patients could be translated directly to the potential treatment of other NSPs-mediated inflammatory diseases. It is gratifying to see that the hard work of all colleagues from academic labs and industry and advocacy in the CatC field may have a clinical payoff.
From the perspective of unmet medical needs, drug repurposing for rare diseases offers a great opportunity. Indeed, rare diseases, not being economically attractive, is not a priority for the majority of the drug industry. There are more than 7,000 rare diseases, and over 95% of them lack an approved therapeutic agent. Drug repositioning would be a particularly attractive approach for rare diseases for both scientific and commercial reasons. A special issue on the topic: "Neutrophil Serine Proteases in Rare Diseases" for Rare Disease and Orphan Drugs Journal will result from the 3rd International Symposium on Cathepsin C IsyCatC III (Tours/France, April 2022).
Submission Deadline31 Aug 2022