Feasibility study for clinical application of caspase-3 inhibitors in Pemphigus vulgaris.

Hariton, William V J; Galichet, Arnaud; Vanden Berghe, Tom; Overmiller, Andrew M; Mahoney, My G; Declercq, Wim; Müller, Eliane J (2017). Feasibility study for clinical application of caspase-3 inhibitors in Pemphigus vulgaris. Experimental dermatology, 26(12), pp. 1274-1277. Blackwell 10.1111/exd.13458

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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 (casp3EKO ) 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.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
05 Veterinary Medicine > Research Foci > DermFocus

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Müller, Eliane Jasmine

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0906-6705

Publisher:

Blackwell

Language:

English

Submitter:

Sandra Nyffenegger

Date Deposited:

01 Feb 2018 16:55

Last Modified:

01 Feb 2018 16:55

Publisher DOI:

10.1111/exd.13458

PubMed ID:

29105150

Uncontrolled Keywords:

Desmoglein 3 Clinical application Pemphigus vulgaris signaling non-apoptotic caspase-3

BORIS DOI:

10.7892/boris.110562

URI:

https://boris.unibe.ch/id/eprint/110562

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