Primidone: a clinically promising candidate for the treatment of psoriasis

Using clinically relevant animal models, we have recently demonstrated that the anticonvulsant primidone (Liskantin^®), approved by the FDA for the treatment of various forms of epilepsy, can effectively block RIPK1 enzymatic activity, which mediates cell death, and consequently prevent RIPK1 cytotoxicity and associated inflammatory responses. Based on these findings, we now reveal both a preventive and, more importantly, a therapeutic effect of primidone in the imiquimod (IMQ)-induced psoriasis-like inflammation model. Notably, the protective effect of IMQ in this necroinflammatory disease is directly correlated with inhibition of the activated state of RIPK1 (as monitored by auto-phosphorylation on Ser166/T169), a critical marker that had been missing in the highly contradictory studies that have previously been published. This allows us to unequivocally identify RIPK1 as a therapeutic target in the treatment of inflammatory disorders, including psoriasis. Given that newly developed RIPK1 inhibitors have shown very limited success in clinical trials for inflammatory and neurological diseases in recent years, and that none of these inhibitors has yet reached clinical utilization, our data strongly recommend a clinical study to evaluate the already approved drug primidone for the treatment of patients suffering from psoriasis within the context of drug repurposing.