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Feasibility study for clinical application of caspase-3 inhibitors in Pemphigus vulgaris.
- Source :
-
Experimental Dermatology . Dec2017, Vol. 26 Issue 12, p1274-1277. 4p. - Publication Year :
- 2017
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *BULLOUS pemphigoid
*SKIN diseases
*CORTIN
*GLUCOCORTICOIDS
*MINERALOCORTICOIDS
Subjects
Details
- Language :
- English
- ISSN :
- 09066705
- Volume :
- 26
- Issue :
- 12
- Database :
- Academic Search Index
- Journal :
- Experimental Dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 126984509
- Full Text :
- https://doi.org/10.1111/exd.13458