Research Overview

Neuroimmunology is the study of inflammation in the nervous system. Virtually all neurological disorders have inflammatory components, and these include diseases traditionally associated with overt inflammation, such as multiple sclerosis (MS), and those previously thought to be purely degenerative, including Alzheimer’s disease. Neuroinflammation originates from the trafficking of several leukocyte subsets into the nervous system and through the production of immune molecules by neural cells themselves. The interaction between leukocytes and neural cells further promotes neuroinflammation and injury. In recent years, reparative properties of neuroinflammation have been appreciated, so that the balance between beneficial and detrimental neuroinflammation is a crucial determinant of outcome. Our research projects have been guided by 3 diseases of the central nervous system (CNS): MS, spinal cord injury (SCI) and brain tumors (malignant gliomas). MS and SCI provide our research program with diseases of chronic and acute neuroinflammation, respectively. In contrast, malignant gliomas present a disease of immunosuppression, whereby the cancer cells neutralize the activity of leukocytes that infiltrate into these tumors. Our research has been translated into Phase III clinical trials in MS and in spinal cord injury (ClinicalTrials.gov Identifier: NCT00666887 and NCT01828203); the Phase III trial in MS has resulted in the demonstration that minocycline reduces the conversion of a first demyelinating event into definite MS (Metz et al., New Engl J Med 376:2122-2133, 2017). Collectively, our studies of neuroimmunology are aimed at understanding, controlling and tipping the balance of neuroinflammation towards one of neuroprotection and regeneration from CNS insults.