Oral Presentation ASDR-AWTRS-MEPSA 2018 Joint Meeting

Harnessing peptide-based therapy to control inflammatory skin diseases (#44)

Anneliese S Ashhurst 1 2 , David M McDonald 1 2 , Cameron C Hanna 1 , Kirstie M Bertram 3 , Hayden Kenny 2 , Sheila Donnelly 4 , Andrew Harman 3 , Scott N Byrne 2 , Richard J Payne 1
  1. School of Chemistry, The University of Sydney, Camperdown, NSW, Australia
  2. Infectious Diseases and Immunology, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
  3. Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, NSW, Australia
  4. School of Life Sciences, Faculty of Science, The University of Technology Sydney, Ultimo, NSW, Australia

There is a growing incidence worldwide of conditions necessitating lifelong immunomodulatory therapy, in settings of autoimmunity, allergy and organ transplantation. Inflammatory skin diseases such as psoriasis, which affects up to 4% of the Western population, can be highly debilitating and places a substantial social and economic burden upon patients. Currently available therapies are not efficacious in all patients and carry a risk of substantial adverse effects. New therapies that provide targeted suppression of inappropriate inflammation are needed. Immunomodulatory peptides offer potential for targeting specific immune pathways with minimal side effects, and have previously been identified from several natural sources. Additionally, peptides can be synthetically produced or modified in a cost-effective manner. We uncovered a novel role for a human peptide (RP23) in modulating and suppressing inflammation. RP23 was produced by chemical synthesis with modifications to enhance bioavailability and efficacy. In vitro culture of murine bone marrow derived macrophages with RP23 led to reduced IL-6 and MCP-1 release after LPS-stimulation, and in primary murine splenic dendritic cells RP23 reduced the secretion of inflammatory chemokines and expression of surface activation markers. In a mouse model of contact dermatitis, a single nanomolar injection of RP23 prior to sensitisation was able to significantly suppress elicitation of inflammation, as measured by a reduction in ear thickness and inflammatory myeloid cell skin infiltrate. Further, in a murine model of imiquimod-induced psoriasis, a single injection of RP23 reduced local erythema, skin thickness and scaling. This immunomodulatory effect was isolated to the area in which RP23 was delivered, unlike topical application of a glucocorticoid which caused systemic immune suppression. When RP23 was injected intra-dermally into healthy human skin explants it reduced spontaneous activation of dermal dendritic cells. RP23 therefore offers potential as a novel, locally acting peptide-based therapy for patients seeking improved management of inflammatory skin diseases.