Several targets in the ubiquitination pathway has attracted interest in the last few years. We are exploring the role of a deubiquitinating (DUB) enzyme in models of neuroinflammation and inflammatory diseases. The target was identified using an in vivo genome-wide discovery platform of randomly mutagenized mice that were screened for the appearance of mutations that protect against acute neuroinflammation using a model of murine cerebral malaria.
This model of neuroinflammation was specifically selected because it is robust and effective, and Dr. Gros' lab previously used it to demonstrate the critical role of certain cytokines (C5a), kinases (JAK3) and transcription factors (STAT1, IRF1, IRF8) in pathological inflammation. Moreover, known risk factors for either MS (IRF8, Themis) or other inflammatory diseases (CCDC88B, Jak3) were detected which correlate to GWAS and eSNP analyses.
We believe that there is space for a novel treatment in neuroinflammatory and inflammatory disorders. As such, we have a novel target involved in epigenetics that shows promising results in the treatment of Multiple Sclerosis (MS) and other inflammatory disorders.