Research Topics
Genomes and Genes | Alastair CompstonSummaryAffiliation: University of Cambridge Country: UK Publications
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Publications
Campath-1H treatment of multiple sclerosisJoanne L Jones
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
Neurodegener Dis 5:27-31. 2008..Here, we summarise our clinical and laboratory findings, describing how this prototypical 'bench to bedside' therapy continues to inform basic science, revealing aspects of the pathogenesis of multiple sclerosis and autoimmunity...- IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H)Joanne L Jones
Department of Clinical Neuroscience, University of Cambridge, Addenbrooke s Hospital, Cambridge, United Kingdom
J Clin Invest 119:2052-61. 2009..We propose that, by driving cycles of T cell expansion and apoptosis to excess, IL-21 increases the stochastic opportunities for T cells to encounter self antigen and, hence, for autoimmunity... - Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunityJoanne L Jones
Department of Clinical Neuroscience, University of Cambridge, Addenbrooke s Hospital, Hills Road, Cambridge, CB2 0QQ, UK
Brain 133:2232-47. 2010.... - New treatment strategies in multiple sclerosisJoanne L Jones
Dept of Clinical Neurosciences, Box 165 Addenbrooke s Hospital, Hills Road, Cambridge, CB2 0QQ, UK
Exp Neurol 225:34-9. 2010..In this review, we first sketch the landscape of novel therapies in multiple sclerosis and then discuss in detail approaches which are likely to emerge over the next few years... - Spotlight on alemtuzumabJ L Jones
Department of Clinical Neurosciences, Box 165, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QQ, UK
Int MS J 16:77-81. 2009..In this review we summarize our experience; describing how this prototypical, "bench-to-bedside" therapy continues to inform basic science, revealing aspects of the pathogenesis of MS and lymphopeniaassociated autoimmunity... - A genome-wide screen for linkage disequilibrium in Sardinian multiple sclerosisFrancesca Coraddu
Neurology Unit, Addenbrooks Hospital, University of Cambridge, Hills Road, Cambridge CB2 2QQ, UK
J Neuroimmunol 143:120-3. 2003..Five of these markers-D2S408 (2q36), D6S271 (6p21), D6S344 (6p25), D7S1818 (7p12) and D16S420 (16p12)-remained nominally significant in both studies after conservative refining analysis... - Abnormal tau phosphorylation in primary progressive multiple sclerosisJane Marian Anderson
Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge, UK
Acta Neuropathol 119:591-600. 2010..These findings establish a platform for further study of the role of insoluble tau formation, including determining the relevance of glial tau pathology, in the neurodegenerative phase of MS... - Refining the analysis of a whole genome linkage disequilibrium association map: the United Kingdom resultsTai Wai Yeo
University of Cambridge Neurology Unit, Addenbrook's Hospital, Hills Road, Cambridge CB2 2QQ, UK
J Neuroimmunol 143:53-9. 2003.... - A high-density screen for linkage in multiple sclerosisStephen Sawcer
University of Cambridge, Department of Clinical Neuroscience, Addenbrooke s Hospital, Hills Road, Cambridge, CB2 2QQ, United Kingdom
Am J Hum Genet 77:454-67. 2005.... - No evidence of a significant role for CTLA-4 in multiple sclerosisRichard H Roxburgh
Department of Clinical Neurosciences, Cambridge University, Addenbrooke s Hospital, CB2 2QQ Cambridge, UK
J Neuroimmunol 171:193-7. 2006..No individual marker or common haplotype showed evidence of association with disease. These data suggest that any effect of CTLA-4 on multiple sclerosis susceptibility is likely to be very small... - CD24 Ala/Val polymorphism and multiple sclerosisAn Goris
Department of Clinical Neurosciences, Neurology Unit, University of Cambridge, Addenbrooke s Hospital, Cambridge CB2 2QQ, UK
J Neuroimmunol 175:200-2. 2006..Since the CD24 gene is part of a segmental duplication, special care is required for the identification and genotyping of single nucleotide polymorphisms... - Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in EuropeansMaria Ban
University of Cambridge, Department of Clinical Neurosciences, Addenbrooke s Hospital, Hills Road, Cambridge, UK
J Neuroimmunol 179:108-16. 2006..Association mapping across the candidate genes implicated by these markers in 937 UK trio families revealed modestly associated haplotypes in JAG1 (p=0.019) on chromosome 20p12.2 and POU2AF1 (p=0.003) on chromosome 11q23.1... - A second major histocompatibility complex susceptibility locus for multiple sclerosisTai Wai Yeo
Department of Clinical Neurosciences, University of Cambridge, Addenbrooke s Hospital, Cambridge, United Kingdom
Ann Neurol 61:228-36. 2007..The possibility that other genes in the MHC independently influence susceptibility to multiple sclerosis has been suggested but remains unconfirmed... - Minimally manipulated oligodendrocyte precursor cells retain exclusive commitment to the oligodendrocyte lineage following transplantation into intact and injured hippocampusDaniel J Webber
Department of Clinical Neurosciences and Centre for Brain Repair, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 2PY, UK
Eur J Neurosci 26:1791-800. 2007..These findings show that unselected and unmanipulated populations of cortical OPCs remain as precursor cells, commit to the oligodendrocyte lineage and fail to respond to the extrinsic cues of a neurogenic or injured environment... - Investigation of the role of mitochondrial DNA in multiple sclerosis susceptibilityMaria Ban
Department of Clinical Neurosciences, University of Cambridge, Addenbrooke s Hospital, Cambridge, United Kingdom
PLoS ONE 3:e2891. 2008..These results add to the evidence suggesting that variation in mtDNA and nuclear encoded mitochondrial genes may contribute to disease susceptibility in multiple sclerosis... - Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosisLisa F Barcellos
Division of Epidemiology, School of Public Health, University of California, Berkeley 94720, USA, and Department of Clinical Neurosciences, University of Cambridge, Addenbrooke s Hospital, UK
Hum Mol Genet 15:2813-24. 2006.... - An experimental model of secondary progressive multiple sclerosis that shows regional variation in gliosis, remyelination, axonal and neuronal lossDavid W Hampton
Cambridge Centre for Brain Repair, University of Cambridge, ED Adrian Building, Forvie Site, Robinson Way, Cambridge, CB2 2PY UK
J Neuroimmunol 201:200-11. 2008..Together with the clinical pattern, our findings identify chronic EAE as an excellent model of secondary progressive multiple sclerosis... - Postnatal astrocytes promote neural induction from adult human bone marrow-derived stem cellsAlexis Joannides
Cambridge Centre for Brain Repair and Department of Neurology, University of Cambridge, Cambridge CB2 2PY, UK
J Hematother Stem Cell Res 12:681-8. 2003..The ability to generate almost limitless numbers of neural precursors from a readily accessible autologous adult human source provides a platform for further studies and potentially has important therapeutic implications... - Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept studyPeter Connick
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
Lancet Neurol 11:150-6. 2012.... - Enhancing linkage analysis of complex disorders: an evaluation of high-density genotypingStephen J Sawcer
University of Cambridge Neurology Unit, Addenbrooke s Hospital, UK
Hum Mol Genet 13:1943-9. 2004..The extent of additional information extracted is considerable, indicating that reanalysis of existing multiplex families using these newer systems would substantially increase power... - A genome wide linkage disequilibrium screen in Parkinson's diseaseThomas Foltynie
Dept of Neurology, University of Cambridge, Cambridge, CB2 2PY, UK
J Neurol 252:597-602. 2005..Subgroup analysis of the most promising marker shows some evidence that microsatellite marker D1S2886 is associated with familial forms of the disease... - Neural stem cells as a potential source of oligodendrocytes for myelin repairSiddharthan Chandran
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
J Neurol Sci 233:179-81. 2005..Inter-species difference in the capacity of neural precursors to generate oligodendrocytes emphasises the need for greater study of human derived stem cell populations... - Common variants near MC4R are associated with fat mass, weight and risk of obesityRuth J F Loos
MRC Epidemiology Unit, Addenbrooke s Hospital, Cambridge CB2 0QQ, UK
Nat Genet 40:768-75. 2008.... - Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factorMaria Ban
Department of Clinical Neuroscience, Addenbrooke s, Hospital, University of Cambridge, Cambridge, UK
Eur J Hum Genet 17:1309-13. 2009.... - A highly enriched niche of precursor cells with neuronal and glial potential within the hair follicle dermal papilla of adult skinDavid P J Hunt
Cambridge Centre for Brain Repair, Cambridge, United Kingdom
Stem Cells 26:163-72. 2008..This strategy of targeting a highly enriched niche of sphere-forming cells provides a novel and efficient method for generating neuronal and glial cells from an accessible adult somatic source that is both defined and minimally invasive... - Tau and alpha-synuclein in susceptibility to, and dementia in, Parkinson's diseaseAn Goris
Department of Clinical Neurosciences Neurology Unit, University of Cambridge, Cambridge, United Kingdom
Ann Neurol 62:145-53. 2007..We investigated the genetic basis of susceptibility to and cognitive heterogeneity of this disease... - Activin/Nodal inhibition alone accelerates highly efficient neural conversion from human embryonic stem cells and imposes a caudal positional identityRickie Patani
Anne McLaren Laboratory for Regenerative Medicine and Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
PLoS ONE 4:e7327. 2009..We therefore sought to investigate the independent influence of SB431542 both on neural commitment of hESCs and positional identity of derived neural progenitors in chemically defined substrate-free conditions... - Myelin repair: the role of stem and precursor cells in multiple sclerosisSiddharthan Chandran
Cambridge Centre for Brain Repair, University of Cambridge, Robinson Way, Cambridge CB2 2PY, UK
Philos Trans R Soc Lond B Biol Sci 363:171-83. 2008..This review considers the basic and clinical biology of remyelination and the potential contribution of stem and precursor cells to enhance and supplement spontaneous remyelination... - Campath-1H treatment of multiple sclerosis: lessons from the bedside for the benchAlasdair Coles
Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 2QQ, UK
Clin Neurol Neurosurg 106:270-4. 2004 - Complexity and heterogeneity in demyelinating diseaseAlastair Compston
Department of Clinical Neurosciences, University of Cambridge Clinical School, Cambridge, CB1 2QQ, UK
Brain 130:1178-80. 2007 - Origins of gliogenic stem cell populations within adult skin and bone marrowDavid P Hunt
Anne Maclaren Laboratory for Regenerative Medicine, MRC Centre for Stem Cell Biology and Regenerative Medicine, Forvie Site, University of Cambridge, Cambridge, United Kingdom
Stem Cells Dev 19:1055-65. 2010..We conclude that SKPs, rather than bone marrow-derived MSCs, represent a more defined and developmentally rational source for the study and generation of Schwann cells from readily accessible adult tissues... - Environmental signals regulate lineage choice and temporal maturation of neural stem cells from human embryonic stem cellsAlexis J Joannides
Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
Brain 130:1263-75. 2007..Controlled manipulation of environmental signals appropriate to the pathological specificity of the targeted disease will be necessary in the design of therapeutic stem cell-based strategies... - Genome-wide association studies in multiple sclerosis: lessons and future prospectsAnu Kemppinen
Neurology Unit, Department of Clinical Neurosciences, University of Cambridge, UK
Brief Funct Genomics 10:61-70. 2011..Finally, many genetic risk variants for MS remain to be identified. In order to expose some of the loci with more modest effects, a GWAS in nearly 10,000 MS patients has recently been completed... - Evidence for abnormal tau phosphorylation in early aggressive multiple sclerosisJane Marian Anderson
Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge, UK
Acta Neuropathol 117:583-9. 2009..The absence of sarcosyl-insoluble tau fraction in early disease and its presence in secondary progression raises the possibility that insoluble tau accumulates with disease progression... - Refining the linkage analysis on chromosome 10 in 449 sib-pairs with multiple sclerosisEva Akesson
Neurology Unit, Addenbrooke s Hospital, University of Cambridge, Cambridge, UK
J Neuroimmunol 143:31-8. 2003..This additional genotyping increased the information extraction in the region from 52% to 79% and revealed increased support for linkage (MLS 2.5) peaking at 10p15... - Induction of Olig2 precursors by FGF involves BMP signalling blockade at the Smad levelBilada Bilican
Department of Clinical Neurosciences and Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom
PLoS ONE 3:e2863. 2008.... - The genetic analysis of multiple sclerosis in Europeans: concepts and designStephen Sawcer
Department of Clinical Neurosciences, Neurology Unit, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 2QQ, UK
J Neuroimmunol 143:13-6. 2003 - A whole genome screen for linkage disequilibrium in multiple sclerosis confirms disease associations with regions previously linked to susceptibilityStephen Sawcer
University of Cambridge Neurology Unit, Addenbrooke's Hospital, Cambridge, UK
Brain 125:1337-47. 2002.... - Multiple sclerosisAlastair Compston
Department of Clinical Neurosciences, University of Cambridge Clinical School, Addenbrooke s Hospital, Cambridge, UK
Lancet 372:1502-17. 2008..We anticipate that future studies in multiple sclerosis will provide a new taxonomy on the basis of mechanisms rather than clinical empiricism, and so inform strategies for improved treatment at all stages of the disease... - The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessmentsPeter Connick
Dept, of Clinical Neurosciences, University of Cambridge, UK
Trials 12:62. 2011..Illustrated by the MSCIMS trial protocol, we describe a novel methodology based on detailed assessment of the anterior visual pathway as a model of wider disease processes--the "sentinel lesion approach"... - Making progress on the natural history of multiple sclerosisAlastair Compston
Department of Clinical Neurosciences University of Cambridge Clinical School, Hills Road, Cambridge, UK
Brain 129:561-3. 2006 - Recurrent myelitis and optic neuritis in a 29-year-old womanAmanda Cox
Department of Clinical Neurosciences, University of Cambridge, UK
Lancet Neurol 4:510-6. 2005 - Association of the truncating splice site mutation in BTNL2 with multiple sclerosis is secondary to HLA-DRB1*15James A Traherne
Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Cambridge, UK
Hum Mol Genet 15:155-61. 2006..The association of BTNL2 with MS observed in the African-American data set was also secondary to the primary DRB1*15 association... - William Ian McDonald: 1933-2006Alastair Compston
Brain Editorial Office, ED Adrian Building, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Cambridge CB20PY, UK
Brain 134:2158-76. 2011..Where possible the date and provenance of material are identified and cited in the text; his curriculum vitae is provided as a supplementary file with individual papers identified by number within each category... - FGF-dependent generation of oligodendrocytes by a hedgehog-independent pathwaySiddharthan Chandran
Cambridge Centre for Brain Repair, University of Cambridge, ED Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK
Development 130:6599-609. 2003..These findings are compatible with the idea of a hedgehog independent pathway for oligodendrocyte generation from neural stem cells... - Different pathways for iNOS-mediated toxicity in vitro dependent on neuronal maturation and NMDA receptor expressionSabine Golde
Cambridge Centre for Brain Repair, University of Cambridge, Cambridge, UK
J Neurochem 82:269-82. 2002..Our results therefore extend existing evidence for NO-mediated toxicity and show a complex interaction between inflammatory and excitotoxic mechanisms of injury in mature neurones... - Efficient generation of neural precursors from adult human skin: astrocytes promote neurogenesis from skin-derived stem cellsAlexis Joannides
Department of Clinical Neurosciences, University of Cambridge and Addenbrooke's Hospital, Cambridge, UK
Lancet 364:172-8. 2004..The generation of almost limitless numbers of neural precursors from a readily accessible autologous adult human source provides a platform for further experimental studies and has potential therapeutic implications... - Oligodendrocytes promote neuronal survival and axonal length by distinct intracellular mechanisms: a novel role for oligodendrocyte-derived glial cell line-derived neurotrophic factorAlastair Wilkins
Cambridge Center for Brain Repair, Forvie Site, Cambridge CB2 2PY, United Kingdom
J Neurosci 23:4967-74. 2003..Therefore, we have shown that factors released by OPCs and oligodendrocytes induce the activation of distinct intracellular pathways within neurons, which have different functional effects on the cell... - A novel role for Sema3A in neuroprotection from injury mediated by activated microgliaHenry H Majed
Department of Clinical Neurosciences, Centre for Brain Repair, University of Cambridge, Forvie Site, Cambridge CB2 2PY, United Kingdom
J Neurosci 26:1730-8. 2006..These results suggest a novel semaphorin-mediated mechanism of neuroprotection whereby stressed neurons can protect themselves from further damage by activated microglia... - Trophic factors attenuate nitric oxide mediated neuronal and axonal injury in vitro: roles and interactions of mitogen-activated protein kinase signalling pathwaysAlastair Wilkins
Department of Clinical Neurosciences and Centre for Brain Repair, University of Cambridge, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK
J Neurochem 92:1487-96. 2005..This study emphasizes that different mechanisms may underlie neuronal/axonal destructive processes, and suggests that trophic factors may modulate NO-mediated neurone/axon destruction via specific pathways... - Multiple sclerosisAlastair Compston
Neurology Unit, University of Cambridge Clinical School, Addenbrooke s Hospital, Cambridge CB2 2QQ, UK
Lancet 359:1221-31. 2002..Despite limited success in each of these categories, everyone touched by multiple sclerosis looks for a better dividend from applying an improved understanding of the pathogenesis to clinical management... - A scaleable and defined system for generating neural stem cells from human embryonic stem cellsAlexis J Joannides
Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, Cambridge, CB2 2PY United Kingdom
Stem Cells 25:731-7. 2007..This system provides a definitive platform for studying human neural development and has potential therapeutic implications... - Oligodendroglial-derived stress signals recruit microglia in vitroRichard Nicholas
University of Cambridge, Neurology Unit, Addenbrookes' Hospital, Hills Road, Cambridge CB2 2QQ, UK
Neuroreport 14:1001-5. 2003..Thus, whilst the initial recruitment of microglia by stressed oligodendroglia may represent part of a survival process engaged by injured cells, this does not necessarily ensure survival... - The pathogenesis and basis for treatment in multiple sclerosisAlastair Compston
School of Clinical Medicine, University of Cambridge Neurology, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QQ, UK
Clin Neurol Neurosurg 106:246-8. 2004.... - Differential generation of oligodendrocytes from human and rodent embryonic spinal cord neural precursorsSiddharthan Chandran
Department of Clinical Neurosciences, University of Cambridge, United Kingdom
Glia 47:314-24. 2004..These results provide further evidence for inter-species difference in the capacity of neural precursors to generate oligodendrocytes... - 'The marvellous harmony of the nervous parts': the origins of multiple sclerosisAlastair Compston
Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital
Clin Med 4:346-54. 2004..Against this background, the sustained epidemic of multiple sclerosis arose when cultural changes led to a subtle but crucial alteration in the age at which genetically vulnerable individuals are exposed to Epstein Barr infection... - Minocycline attenuates nitric oxide-mediated neuronal and axonal destruction in vitroAlastair Wilkins
Centre for Brain Repair and Dept of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK
Neuron Glia Biol 1:297-305. 2004..These results indicate that, in addition to anti-inflammatory properties, minocycline has direct protective effects on neurons and provides further evidence for its use in disorders of the CNS... - Genetic analysis of multiple sclerosisAlastair Compston
University of Cambridge Neurology Unit, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom
Curr Neurol Neurosci Rep 2:259-66. 2002..When eventually in place, the potential of this genetic knowledge for improved understanding of the pathogenesis of multiple sclerosis and designing novel treatments is considerable...