Publication
Title
Feasibility study for clinical application of caspase-3 inhibitors in Pemphigus vulgaris
Author
Abstract
The potentially severe side effects of systemic corticosteroids and immunosuppressants used in Pemphigus vulgaris (PV) call for novel therapeutic approaches. In this context, pharmacological inhibition of major pathogenic signalling effectors represents a promising alternative. However, we have also shown that overinhibition of effectors required for epidermal homeostasis can exacerbate PV pathophysiology implicating transepidermal keratinocyte fragility. A feedforward target validation therefore preferentially includes studies on knockout mouse models. We previously reported on successful amelioration of PV blisters following inhibition of non-apoptotic, low-level caspase-3. Here, we use conditional, keratinocyte-specific caspase-3-deficient mice (casp3(EKO)) to demonstrate (i) absence of keratinocyte fragility upon injection of the potent Dsg3-specific antibody AK23 and (ii) amelioration of blistering on the background of known signalling effectors. Our results provide the experimental proof of concept justifying translation of the caspase-3 inhibitor approach into PV clinical trials.
Language
English
Source (journal)
Experimental dermatology. - Copenhagen
Publication
Copenhagen : 2017
ISSN
0906-6705
Volume/pages
26 :12 (2017) , p. 1274-1277
ISI
000419225400021
Full text (Publisher's DOI)
UAntwerpen
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 18.10.2018
Last edited 06.09.2021