Associate Neurologist, Division of Neurocritical Care and Cerebrovascular Diseases, Department of Neurology, Brigham and Women’s Hospital
Head, Immunology of Brain Injury Program, Ann Romney Center for Neurologic Diseases
Assistant Professor of Neurology, Harvard Medical School
Targeting Neuroinflammation by Nasal Anti-CD3 to Improve Functional Recovery in Traumatic Spinal Cord Injury
Traumatic spinal cord injury (SCI) is a debilitating condition that significantly impacts individuals and places a heavy burden on healthcare systems. Currently, no effective treatments are available to enhance a patient’s recovery or improve outcomes. When SCI occurs, the body induces a complex neuroinflammatory response, characterized by microglia and leukocyte activation. While microglial inflammation plays a crucial role in recovery, it can also contribute to further damage by exacerbating spinal cord edema, axonal degeneration, and neuronal cell death.
Saef Izzy, MD, FNCS, and his team have discovered that nasally administered anti-CD3 monoclonal antibody triggers an anti-inflammatory immune response that helps reduce neuroinflammation in the central nervous system (CNS). In this process, the production of IL-10-secreting regulatory T cells is increased in the cervical lymph nodes, which then move to the CNS to help suppress microglia neuroinflammation. Preliminary data in animal models of SCI have shown that nasal anti-CD3 decreases microglial activation and improves motor function after injury.
With the Stepping Strong Breakthrough Award, Dr. Izzy aims to investigate further how nasal anti-CD3-induced regulatory T cells mitigate spinal cord microglia activation and enhance functional recovery in SCI.
Saef Izzy, MD, FNCS, is an assistant professor of neurology at Harvard Medical School and an associate neurologist in the Division of Neurocritical Care and Cerebrovascular Diseases at Brigham and Women’s Hospital. Dr. Izzy attended the University of Baghdad College of Medicine, completed his residency at the University of Massachusetts Medical School, and pursued a fellowship at Mass General Brigham. After finishing his clinical training, Dr. Izzy established his laboratory which centers on understanding the underlying immune mechanisms associated with acute brain injury outcomes and their response to therapy. Within the lab, he aims to identify novel biomarkers and therapeutics that target the immune response and improve neurological outcomes after disease or injury. Dr. Izzy’s laboratory interests include immunoregulation in acute neurological disease, mucosal immunology, microglia, gut-brain axis, and immune mechanisms in other neurological disorders, including post-traumatic epilepsy and neurodegenerative diseases.