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SUMMARY:Multiple sclerosis\, depleting lymphocytes and autoimmunity - Revd
 . Dr. Alasdair Coles\, Department of Clinical Neurosciences\, Cambridge
DTSTART:20090930T104500Z
DTEND:20090930T111500Z
UID:TALK18697@talks.cam.ac.uk
CONTACT:Hannah Critchlow
DESCRIPTION:This talk is part of the Cambridge Clinical Neuroscience and M
 ental Health Symposium\, 29th - 30th September 2009 at West Road Concert H
 all. This event is free to attend for cambridge neuroscientists although r
 egistration is required. To register\, and for further information\, pleas
 e visit: http://www.neuroscience.cam.ac.uk/cnmhs/\n\nAbstract: 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 earl
 y work in secondary progressive MS demonstrated its efficacy in suppressin
 g relapses and MRI inflammatory activity in the brain\, however patients' 
 disability continued to progress. So we tried alemtuzumab in early relapsi
 ng-remitting multiple sclerosis. Compared to the standard therapy\, interf
 eron beta-1a\, alemtuzumab reduced by over 70% both the relapse rate and t
 he 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 trial
 s are now on-going\, testing alemtuzumab in treatment-naive and treatment-
 experienced MS patients.\nDespite the prolonged lymphopenia\, patients do 
 not get opportunistic infections. But\, 30% of our patients develop autoim
 munity\, mainly against the thyroid and rarely against platelets\, months 
 or years after alemtuzumab treatment. This is found in patients who have p
 articularly high rates of lymphocyte proliferation and apoptosis after ale
 mtuzumab. This state of high lymphocyte cell-cycling is found in individua
 ls who are genetically programmed to secrete high levels of the cytokine I
 L-21. This may have implications for other forms of autoimmunity.\n
LOCATION:West Road Concert Hall
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