Professor Alasdair Coles University positionProfessor Professor Alasdair Coles is pleased to consider applications from prospective PhD students. DepartmentsDepartment of Clinical Neurosciences InstitutesHome pagehttps://www-neurosciences.medschl.cam.ac.uk/jones-c... Research ThemeInterestsWe study people with immunological illnesses of the brain, especially multiple sclerosis. Our most important work to date has been on alemtuzumab (Campath-1H), a humanised monoclonal antibody made originally in Cambridge. We started using it to treat multiple sclerosis in1991. In September 2013, alemtuzumab received its European license and in 2014 it was approved by the FDA and by NICE. We are also doing a trial of a potential remyelinating therapy in multiple sclerosis, and doing a pilot study of immunotherapy in people with psychosis associated with anti-neuronal antibodies. Research Focus
EquipmentCell culture Randomised control trials Collaborators
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Key publicationsJones JL, Thompson SA, Loh P, Davies JL, Tuohy OC, Curry AJ, Azzopardi L, Hill-Cawthorne G, Fahey MT, Compston A, Coles AJ (2013), “Human autoimmunity after lymphocyte depletion is caused by homeostatic T-cell proliferation.” Proc Natl Acad Sci U S A 110(50):20200-5 Details McCarthy CL, Tuohy O, Compston DA, Kumararatne DS, Coles AJ, Jones JL (2013), “Immune competence after alemtuzumab treatment of multiple sclerosis.” Neurology 81(10):872-6 PDF Details Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DA, CARE-MS I investigators (2012), “Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial.” Lancet 380(9856):1819-28 PDF Details Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Miller T, Fisher E, Sandbrink R, Lake SL, Margolin DH, Oyuela P, Panzara MA, Compston DA, CARE-MS II investigators (2012), “Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial.” Lancet 380(9856):1829-39 PDF Details Jones JL, Anderson JM, Phuah CL, Fox EJ, Selmaj K, Margolin D, Lake SL, Palmer J, Thompson SJ, Wilkins A, Webber DJ, Compston DA, Coles AJ (2010), “Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity.” Brain 133(Pt 8):2232-47 PDF Details Somerfield J, Hill-Cawthorne GA, Lin A, Zandi MS, McCarthy C, Jones JL, Willcox M, Shaw D, Thompson SA, Compston AS, Hale G, Waldmann H, Coles AJ (2010), “A novel strategy to reduce the immunogenicity of biological therapies.” J Immunol 185(1):763-8 PDF Details Thompson SA, Jones JL, Cox AL, Compston DA, Coles AJ (2010), “B-cell reconstitution and BAFF after alemtuzumab (Campath-1H) treatment of multiple sclerosis.” J Clin Immunol 30(1):99-105 Details Jones JL, Phuah CL, Cox AL, Thompson SA, Ban M, Shawcross J, Walton A, Sawcer SJ, Compston A, Coles AJ (2009), “IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H).” J Clin Invest 119(7):2052-61 PDF Details CAMMS223 Trial Investigators, Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK (2008), “Alemtuzumab vs. Interferon beta-1a in early multiple sclerosis.” N Engl J Med 359(17):1786-801 PDF Details Compston DAS, Coles AJ (2008), “Multiple Sclerosis” Lancet 372: 1502-1517 Coles AJ, Cox A, Le Page E, Jones J, Trip SA, Deans J, Seaman S, Miller DH, Hale G, Waldmann H, Compston DA (2006), “The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy.” J Neurol 253(1):98-108 Details Coles AJ, Thompson S, Cox AL, Curran S, Gurnell EM, Chatterjee VK (2005), “Dehydroepiandrosterone replacement in patients with Addison's disease has a bimodal effect on regulatory (CD4+CD25hi and CD4+FoxP3+) T cells” Eur J Immunol 35(12):3694-703 Details Cox AL, Thompson SA, Jones JL, Robertson VH, Hale G, Waldmann H, Compston DA, Coles AJ (2005), “Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis” Eur J Immunol 35(11):3332-42 Details Coles AJ, Wing M, Smith S, Coraddu F, Greer S, Taylor C, Weetman A, Hale G, Chatterjee VK, Waldmann H, Compston A (1999), “Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis.” Lancet 354(9191):1691-5 Details Coles AJ, Wing MG, Molyneux P, Paolillo A, Davie CM, Hale G, Miller D, Waldmann H, Compston A (1999), “Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis.” Ann Neurol 46(3):296-304 Details Publications2014Azzopardi L, Thompson SA, Harding KE, Cossburn M, Robertson N, Compston A, Coles AJ, Jones JL (2014), “Predicting autoimmunity after alemtuzumab treatment of multiple sclerosis.” J Neurol Neurosurg Psychiatry 85(7):795-8 Details Brown JW, Martin PJ, Thorpe JW, Michell AW, Coles AJ, Cox AL, Vincent A, Zandi MS (2014), “Long-term remission with rituximab in refractory leucine-rich glioma inactivated 1 antibody encephalitis.” J Neuroimmunol 271(1-2):66-8 Details Coles AJ, Compston A, 70 signatories (2014), “Product licences for alemtuzumab and multiple sclerosis.” Lancet 383(9920):867-8 Details Jones JL, Coles AJ (2014), “Mode of action and clinical studies with alemtuzumab.” Exp Neurol Details 2013Abrahamsson SV, Angelini DF, Dubinsky AN, Morel E, Oh U, Jones JL, Carassiti D, Reynolds R, Salvetti M, Calabresi PA, Coles AJ, Battistini L, Martin R, Burt RK, Muraro PA (2013), “Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis.” Brain 136(Pt 9):2888-903 Details Brown J, Coles A, Jones J (2013), “First use of alemtuzumab in Balo's concentric sclerosis: a case report.” Mult Scler Details Brown JW, Coles AJ (2013), “Alemtuzumab: evidence for its potential in relapsing-remitting multiple sclerosis.” Drug Des Devel Ther 7:131-8 Details Coles AJ (2013), “Alemtuzumab treatment of multiple sclerosis.” Semin Neurol 33(1):66-73 Details Coles AJ (2013), “Alemtuzumab therapy for multiple sclerosis.” Neurotherapeutics 10(1):29-33 Details Kousin-Ezewu O, Coles A (2013), “Alemtuzumab in multiple sclerosis: latest evidence and clinical prospects.” Ther Adv Chronic Dis 4(3):97-103 Details Williams T, Coles A, Azzopardi L (2013), “The outlook for alemtuzumab in multiple sclerosis.” BioDrugs 27(3):181-9 Details 2012Button T, Altmann D, Tozer D, Dalton C, Hunter K, Compston A, Coles A, Miller D (2012), “Magnetization transfer imaging in multiple sclerosis treated with alemtuzumab.” Mult Scler Details Coles A (2012), “We are about to cure MS in the next 10 years, even though we do not know its cause: no.” Mult Scler 18(6):784-5 Details Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Skoromets A, Stolyarov I, Bass A, Sullivan H, Margolin DH, Lake SL, Moran S, Palmer J, Smith MS, Compston DA (2012), “Alemtuzumab more effective than interferon ?-1a at 5-year follow-up of CAMMS223 Clinical Trial.” Neurology 78(14):1069-78 Details Costelloe L, Jones J, Coles A (2012), “Secondary autoimmune diseases following alemtuzumab therapy for multiple sclerosis.” Expert Rev Neurother 12(3):335-41 Details Hill-Cawthorne GA, Button T, Tuohy O, Jones JL, May K, Somerfield J, Green A, Giovannoni G, Compston DA, Fahey MT, Coles AJ (2012), “Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis.” J Neurol Neurosurg Psychiatry 83(3):298-304 Details Lennox BR, Coles AJ, Vincent A (2012), “Antibody-mediated encephalitis: a treatable cause of schizophrenia.” Br J Psychiatry 200:92-4 Details Rieckmann P, Boyko A, Centonze D, Coles A, Elovaara I, Havrdová E, Hommes O, Lelorier J, Morrow SA, Oreja-Guevara C, Rijke N, Schippling S (2012), “Future MS care: a consensus statement of the MS in the 21st Century Steering Group.” J Neurol Details 2011Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Bass AD, Wynn DR, Margolin DH, Lake SL, Moran S, Palmer J, Smith MS, Compston DA (2011), “Alemtuzumab versus interferon beta-1a in early relapsing-remitting multiple sclerosis: post-hoc and subset analyses of clinical efficacy outcomes.” Lancet Neurol 10(4):338-48 Details Cossburn M, Pace AA, Jones J, Ali R, Ingram G, Baker K, Hirst C, Zajicek J, Scolding N, Boggild M, Pickersgill T, Ben-Shlomo Y, Coles A, Robertson NP (2011), “Autoimmune disease after alemtuzumab treatment for multiple sclerosis in a multicenter cohort.” Neurology 77(6):573-9 Details Cuker A, Coles AJ, Sullivan H, Fox E, Goldberg M, Oyuela P, Purvis A, Beardsley DS, Margolin DH (2011), “A distinctive form of immune thrombocytopenia in a phase 2 study of alemtuzumab for the treatment of relapsing-remitting multiple sclerosis.” Blood 118(24):6299-305 Details Jones JL, Dean AF, Antoun N, Scoffings DJ, Burnet NG, Coles AJ (2011), “'Radiologically compatible CLIPPERS' may conceal a number of pathologies.” Brain 134(Pt 8):e187 Details Laguna Goya R, Busch R, Mathur R, Coles AJ, Barker RA (2011), “Human fetal neural precursor cells can up-regulate MHC class I and class II expression and elicit CD4 and CD8 T cell proliferation.” Neurobiol Dis 41(2):407-14 Details Shah AJ, Breen DP, Thomas D, Cross J, Coles A, Molyneux P (2011), “An evolving case of headaches and strokes.” Pract Neurol 11(2):113-7 Details 2010Jones JL, Coles AJ (2010), “New treatment strategies in multiple sclerosis.” Exp Neurol 225(1):34-9 Details Marsh EA, Hirst CL, Llewelyn JG, Cossburn MD, Reilly MM, Krishnan A, Doran M, Ryan AM, Coles AJ, Jones JL, Robertson NP (2010), “Alemtuzumab in the treatment of IVIG-dependent chronic inflammatory demyelinating polyneuropathy.” J Neurol Details Schoenmakers E, Agostini M, Mitchell C, Schoenmakers N, Papp L, Rajanayagam O, Padidela R, Ceron-Gutierrez L, Doffinger R, Prevosto C, Luan J, Montano S, Lu J, Castanet M, Clemons N, Groeneveld M, Castets P, Karbaschi M, Aitken S, Dixon A, Williams J, Campi I, Blount M, Burton H, Muntoni F, O'Donovan D, Dean A, Warren A, Brierley C, Baguley D, Guicheney P, Fitzgerald R, Coles A, Gaston H, Todd P, Holmgren A, Khanna KK, Cooke M, Semple R, Halsall D, Wareham N, Schwabe J, Grasso L, Beck-Peccoz P, Ogunko A, Dattani M, Gurnell M, Chatterjee K (2010), “Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans.” J Clin Invest 120(12):4220-35 Details Zandi MS, Irani SR, Lang B, Waters P, Jones PB, McKenna P, Coles AJ, Vincent A, Lennox BR (2010), “Disease-relevant autoantibodies in first episode schizophrenia.” J Neurol Details 2009Coles A (2009), “Trials of diminishing relapses for diminishing returns.” Lancet Neurol 8(10):870-1 Details Coles A (2009), “Multiple sclerosis.” Pract Neurol 9(2):118-26 Details Jones J, Coles A (2009), “Spotlight on alemtuzumab.” Int MS J 16(3):77-81 Details 2008Compston A, Coles A (2008), “Multiple sclerosis.” Lancet 372(9648):1502-17 Details Jones JL, Coles AJ (2008), “Campath-1H treatment of multiple sclerosis.” Neurodegener Dis 5(1):27-31 Details 2007Coles A (2007), “The fragile benefit of BENEFIT.” Lancet Neurol 6(9):753-4 Details Coles, A. and Compston, A (2007), “Antibody Therapy of Multiple Sclerosis” in Waldmann, H. (ed.), Monoclonal Antibodies as Therapeutic Agents: Fundamentals, Therapeutic Applications and Latest Advances, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London http://www.hstalks.com/?t=BL0471264-Coles Simpson BS, Coles AJ (2007), “Rationale for cytotoxic monoclonal antibodies in MS.” Int MS J 14(2):48-56 Details Zandi MS, Coles AJ (2007), “Notes on the kidney and its diseases for the neurologist.” J Neurol Neurosurg Psychiatry 78(5):444-9 Details 2006Coles A (2006), “The curious incident of disability in multiple sclerosis trials.” Lancet Neurol 5(11):899-900 Details Cox AL, Coles AJ, Nortje J, Bradley PG, Chatfield DA, Thompson SJ, Menon DK (2006), “An investigation of auto-reactivity after head injury.” J Neuroimmunol 174(1-2):180-6 Details 2004Coles A, Dick D (2004), “Unilateral calf hypertrophy.” J Neurol Neurosurg Psychiatry 75(11):1606 Details Harkness KA, Coles A, Pohl U, Xuereb JH, Baron JC, Lennox GG (2004), “Rapidly reversible dementia in cerebral amyloid inflammatory vasculopathy.” Eur J Neurol 11(1):59-62 Details 2003Coles A, Mukherjee M, Compston A (2003), “Case reports in The Lancet.” Lancet 361(9364):1230 Details Golde S, Coles A, Lindquist JA, Compston A (2003), “Decreased iNOS synthesis mediates dexamethasone-induced protection of neurons from inflammatory injury in vitro.” Eur J Neurosci 18(9):2527-37 Details 2002Coles AJ (2002), “Neutralising antibodies to the beta interferons.” J Neurol Neurosurg Psychiatry 73(2):110-1 Details 2001Broadley SA, Sawcer SJ, Chataway SJ, Coraddu F, Coles A, Gray J, Roxburgh R, Clayton D, Compston DA (2001), “No association between multiple sclerosis and the Notch3 gene responsible for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).” J Neurol Neurosurg Psychiatry 71(1):97-9 Details Coles A, Barker R (2001), “A case of stiff limb syndrome responsive to plasma exchange.” J Neurol Neurosurg Psychiatry 70(3):407-8 Details Coles A, Deans J, Compston A (2001), “Multiple sclerosis treatment trial precipitates divorce.” J Neurol Neurosurg Psychiatry 70(1):135 Details 2000Coles A (2000), “Neurologic complications in organ transplant recipients” J Neurol Neurosurg Psychiatry 68(1):123C Details 1999Coles A (1999), “Hospitalist neurology. Blue books of practical neurology” J Neurol Neurosurg Psychiatry 67(5):699F Details Coles A (1999), “Systemic diseases, part II” J Neurol Neurosurg Psychiatry 67(5):699D Details Paolillo A, Coles AJ, Molyneux PD, Gawne-Cain M, MacManus D, Barker GJ, Compston DA, Miller DH (1999), “Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath 1H.” Neurology 53(4):751-7 Details 1998Coles AJ, Wing MG, Compston DA (1998), “Disease activity and the immune set in multiple sclerosis: blood markers for immunotherapy.” Mult Scler 4(3):232-8 Details Gawne-Cain ML, O'Riordan JI, Coles A, Newell B, Thompson AJ, Miller DH (1998), “MRI lesion volume measurement in multiple sclerosis and its correlation with disability: a comparison of fast fluid attenuated inversion recovery (fFLAIR) and spin echo sequences.” J Neurol Neurosurg Psychiatry 64(2):197-203 Details Tubridy N, Coles AJ, Molyneux P, Compston DA, Barkhof F, Thompson AJ, McDonald WI, Miller DH (1998), “Secondary progressive multiple sclerosis: the relationship between short-term MRI activity and clinical features.” Brain 121 ( Pt 2):225-31 Details 1996Moreau T, Coles A, Wing M, Isaacs J, Hale G, Waldmann H, Compston A (1996), “Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis.” Brain 119 ( Pt 1):225-37 Details Moreau T, Coles A, Wing M, Thorpe J, Miller D, Moseley I, Issacs J, Hale G, Clayton D, Scolding N, Waldmann H, Compston A (1996), “CAMPATH-IH in multiple sclerosis.” Mult Scler 1(6):357-65 Details |