Calcium dysregulation and oxidative stress: from molecular mechanisms to therapeutic implications in Hailey-Hailey disease

HHD is a rare hereditary skin disease; there is no cure and treatment is aimed at reducing symptoms. Our studies employing primary human KC derived from HHD-patients clearly support a role for ROS in HHD symptoms manifestation. The suggestion is that disturbances in the oxidant antioxidant system in the skin play an important role in the pathogenesis of HHD disease. Thus, we hypothesize that an antioxidant treatment might provide a novel therapeutic approach for patients with HHD. In our preliminary results we describe the responses of two patients with Hailey-Hailey disease to a sustained resorbable implant formulation of afamelanotide, a well-known compound with potent protective and antioxidative effects. In both patients a complete remission was obtained after 2 months (see preliminary results), and this clinical improvement was maintained after treatment. Quality of life was significantly improved, as shown by the application of the Medical Outcome Survey Short-Form 36 (SF-36). Our observations suggest that antioxidant treatment has beneficial effects in patients affected by HHD. We are rapidly closing in on defining its signaling pathways and its biological functions in rescuing ROS defects using HHD-derived primary KC. We believe that our discoveries will allow after a larger confirmation trials to convert our experimental approach into successful therapeutic protocol.