Antibodies Targeting Gasdermin E as a Potential Therapeutic Option for Psoriasis – A Pilot Study on a Mouse Model

Julia Nowowiejska-Purpurowicz,1 Justyna M Hermanowicz,2 Dariusz Pawlak,2 Iwona Flisiak,1,* Tomasz Lipinski3,* 1Department of Dermatology and Venereology, Medical University of Bialystok, Bialystok, 15-540, Poland; 2Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, 15-222, Poland; 3Lukasiewicz Research Network - PORT Polish Center for Technology Development, Wrocław, 54-066, Poland*These authors contributed equally to this workCorrespondence: Julia Nowowiejska-Purpurowicz, Department of Dermatology and Venereology, Medical University of Bialystok, Zurawia 14 Street, Bialystok, 15-540, Poland, Email [email protected]: Psoriasis is a frequent and complex dermatosis of uncertain origin. A few years ago, a family of gasdermin proteins was implicated in psoriasis pathogenesis. Although the number of therapeutic options for psoriasis is growing, considering the burden of the disease, treatment personalization, and the possibility of side effects or loss of the drug’s efficacy, it is important to seek new therapeutic targets.Objective: The aim of this study was to assess the efficacy of antibodies against gasdermin E (GSDME) in the treatment of psoriatic lesions.Methods: The study involved 30 male BALB/c mice, 8 weeks old. 5% imiquimod cream was applied topically on the skin to induce psoriatic lesions. The next day after the psoriatic lesions appeared, the antibodies were administered. Mice from the study group received the rabbit polyclonal anti-GSDME antibody intravenously or intraperitoneally. The control group was administered sterile 0.9% saline solution.Results: The injection of anti-GSDME antibodies to mice with imiquimod-induced psoriasis resulted in the resolution of skin lesions, whereas the injection of saline to the control group did not result in significant changes.Conclusion: Antibodies targeting GSDME seem to be promising therapeutic agents in psoriasis; however, their utility has to be confirmed in future studies.Plain Language Summary: Psoriasis is a frequent and incurable skin disease that affects approximately 125 million people worldwide. It is characterized by chronic inflammation, wide comorbidity, and decreased life expectancy. The study was carried out by authorized personnel in the Experimental Medicine Center, Medical University of Bialystok, Poland. The aim of the study was to look for a new medication for psoriasis and test the utility of antibodies that bind a protein called gasdermin E (GSDME), and hence, inhibit GSDME’s role in psoriasis. This is a pre-clinical experiment on 30 mice with psoriasis, which was previously induced by a cream with imiquimod. Subsequently, 20 mice received a polyclonal rabbit anti-GSDME antibody, which was injected intravenously and intraperitoneally, whereas 10 mice received saline solution (no active compound). The injection of an antibody against GSDME to mice with imiquimod-induced psoriasis lead to the resolution of skin lesions, whereas mice that received saline solution did not heal. Antibodies targeting GSDME seem to be a promising future medication in psoriasis.Keywords: psoriasis, gasdermin, gasdermin E, GSDME, mouse model, antibody