Pharmacological block of the prokineticin system and of microglia activation to treat pain and mood disorders in Fabry-Anderson disease

Pain accompanies Fabry patients during all their life. Analgesic drugs are not fully effective, and even specific therapies, such as ERT and migalastat, do not successfully relief pain. Moreover the presence of pain is often related to the development of mood alterations with depression and anxiety. In the last years scientific research on chronic pain with characteristics similar to that of Fabry patients, has demonstrated that its onset is due to the presence of neuroinflammation, that is the activation in the nervous system of non-neuronal cells such as microglia and astrocytes. They produce cytokines and chemokines which sustain and amplify the pain sensation. Pharmacological treatments able to decrease neuroinflammation have been shown to be effective in relieving pain of different origins. In this project we want to  validate pharmacological treatments that modulate neuroinflammation and treat pain in a model of Fabry, a genetically modified mouse frequently utilized in Fabry preclinical research. We will try two approaches. We will use the antibiotic minocycline, in clinic since many years, and recently discovered to switch off microglia activation and repurposed as pain killer. As second alternative, we will focus on prokineticins, a novel family of mediators with a recognized  role as proinflammatory and pronociceptive molecules. The antagonism of prokineticins has a strong analgesic effect. Besides pain, we will also evaluate the effect of treatments on depressive and anxiety symptoms. In conclusion this study will lead to the identification of new and better treatment for controlling pain and related psychic alterations in Fabry patients.