28 Apr Potential Novel Therapeutic Target For Psoriasis Identified

MedicalResearch.com Interview with:

Prof. Rudi Beyaert

Professor Rudi Beyaert
VIB – Inflammation Research Center Ghent University
Department for Biomedical Molecular Biology Unit of Molecular Signal Transduction in Inflammation
Technologiepark Ghent) Belgium 

MedicalResearch.com: What is the background for this study? What are the main findings?

Prof. Beyaert: The interest of my laboratory is in understanding the molecular mechanisms that are responsible for the development of inflammatory diseases such as Crohn’s disease, multiple sclerosis, rheumatoid arthritis and also psoriasis, which is the topic of the published study. We already know that genetic factors can determine the onset of these inflammatory diseases, but how these genetic factors drive an inflammatory response is still largely unclear. We were specifically interested in the CARD14 gene, because patients with mutations in CARD14 have a very high chance to develop psoriasis. Psoriasis-associated mutations in CARD14 trigger specific skin cells (keratinocytes) to produce and release large amounts of other proteins that recruit and activate specific white blood cells driving an inflammatory response. We now discovered that this effect is dependent on the physical interaction of CARD14 with the protease MALT1 in keratinocytes, leading to the activation of its enzymatic activity and the MALT1-mediated cleavage and inactivation of a number of cellular proteins that normally keep our immune system in check. Treatment of skin cells with small compound MALT1 inhibitors prevents the CARD14-induced production of several pro-inflammatory mediators.

MedicalResearch.com: What should clinicians and patients take away from your report?

Prof. Beyaert: Our findings indicate MALT1 as a novel therapeutic target in psoriasis and we are already actively developing and testing several MALT1 inhibitors as a potential novel treatment for psoriasis. Unfortunately, it will still take many years of further research before MALT1 inhibitors can enter the clinic.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Prof. Beyaert: It should be mentioned that the mechanism we revealed applies to psoriasis that is due to mutations in CARD14. If MALT1 mediates also other types of psoriasis is currently under investigation. Also, in order to have a better view on possible side effects of the inhibition of CARD14/MALT1 activities, It will be very important to better understand the physiological function of CARD14/MALT1 in healthy patients. 

MedicalResearch.com: Is there anything else you would like to add?

Prof. Beyaert: Findings as ours and many other colleagues around the world illustrate that a better understanding of the molecular basis of psoriasis and other autoimmune diseases is key to the development of novel therapeutic approaches. 

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Inna S Afonina, Elien Van Nuffel, Griet Baudelet, Yasmine Driege, Marja Kreike, Jens Staal, Rudi Beyaert.The paracaspase MALT1 mediates CARD14-induced signaling in keratinocytes. EMBO Reports, April 2016 DOI: 15252/embr.201642109

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Last Updated on April 28, 2016 by Marie Benz MD FAAD