PROJECT: JTC2014: Neuro-IFN

Aicardi-GoutiŠres syndrome (AGS) is a Mendelian inflammatory disorder particularly affecting the brain, occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1 or IFIH1. In the disease state, it is hypothesised that endogenously produced nucleic acids, normally metabolized by the AGS-associated proteins, trigger a type I interferon innate immune response. AGS is associated with significant morbidity and a high risk of death, so that an improved understanding of disease pathogenesis is urgently needed for the development of rational treatments. Making use of a unique set of reagents, we wish to define the neuroinflammatory process occurring in AGS patients. These investigations will have relevance to other type I interferonopathies, HIV-1 associated encephalopathy and the neurological sequelae of systemic lupus erythematosus.