Abstract

This talk is part of the Cambridge Clinical Neuroscience and Mental Health Symposium, 29th – 30th September 2009 at West Road Concert Hall. This event is free to attend for cambridge neuroscientists although registration is required. To register, and for further information, please visit: http://www.neuroscience.cam.ac.uk/cnmhs/

Abstract: Since 1991, we have been using alemtuzumab (Campath-1H) as an experimental treatment of multiple sclerosis. This humanised monoclonal antibody depletes T and B lymphocytes and then they reconstitute, over months and years. Our early work in secondary progressive MS demonstrated its efficacy in suppressing relapses and MRI inflammatory activity in the brain, however patients’ disability continued to progress. So we tried alemtuzumab in early relapsing-remitting multiple sclerosis. Compared to the standard therapy, interferon beta-1a, alemtuzumab reduced by over 70% both the relapse rate and the risk of sustaining fixed disability the rate of sustained accumulation of disability. Unexpectedly, the mean disability of the alemtuzumab group actually improved and their MRI brain volume increased from months 12-36, but showed continued atrophy in the interferon-beta group. Phase 3 trials are now on-going, testing alemtuzumab in treatment-naive and treatment-experienced MS patients. Despite the prolonged lymphopenia, patients do not get opportunistic infections. But, 30% of our patients develop autoimmunity, mainly against the thyroid and rarely against platelets, months or years after alemtuzumab treatment. This is found in patients who have particularly high rates of lymphocyte proliferation and apoptosis after alemtuzumab. This state of high lymphocyte cell-cycling is found in individuals who are genetically programmed to secrete high levels of the cytokine IL-21. This may have implications for other forms of autoimmunity.