JON_Suppl_Abstract_02_06 05.05.2006 10:42 Uhr Seite 1
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`J Neurol (2006) 253 [Suppl 2]: II/1–II/170
`DOI 10.1007/s00415-006-2001-2
`
`Sixteenth Meeting of the
`European Neurological Society
`27–31 May 2006, Lausanne, Switzerland
`Symposia and Free Communications
`
`The abstracts have been reviewed by:
`Z. Argov, O. A. Bajenaru, J. Bogousslavsky, O. Combarros, G. Comi,V. Dietz,
`M. Donaghy, C. Elger, J. M. Ferro, C. Krarup, I. Milonas, G. Moonen,
`Y. Parman,V. Planté-Bordeneuve, G. Said, E. Scarpini, R. Soffietti,
`E. Schmutzhard, A. Steck, E. Tolosa, J.Valls-Solé, M. J. D.Vidailhet
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`Page 1 of 2
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`JON_Suppl_Abstract_02_06 05.05.2006 10:42 Uhr Seite 27
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`Session 14
`
`Multiple sclerosis 4
`
`O106
`Myelin basic protein-T cell lines from patients with multiple sclerosis ex-
`press high affinity full-length BDNF receptor: implications for T-cell sur-
`vival
`L. De Santi, L. Cantalupo, C. Cioni, P. Annunziata
`University of Siena (Siena, I)
`
`Objectives: Brain-derived neurotrophic factor (BDNF), a neurotrophin de-
`termining neuronal survival during development and repair, is primarily
`produced by neurons. However, immunocompetent cells, including T cells,
`produce BDNF in inflammatory lesions of multiple sclerosis (MS) brains,
`suggesting a role for BDNF in neuroprotective inflammation in MS. To date,
`there are conflicting data about the ability of immunocompetent cells to ex-
`press gp145trkB, the high affinity full-length BDNF receptor, in MS. Aim of
`our study was to evaluate the expression of gp145trkB by CD3 + T lympho-
`cytes,monocytes,lymphoblastoid B cell lines (B-LCLs),myelin basic protein
`(MBP)-T cell lines from patients with MS and its functional role in MBP-au-
`toreactive T cell line survival.
`Material and methods: Peripheral blood mononuclear cells (PBMCs)
`were obtained from 48 MS patients,34 with relapsing-remitting (RRMS) and
`14 with secondary progressive MS (SPMS) and from 15 sex- and age-
`matched healthy subjects (HS). T lymphocytes and monocytes were stimu-
`lated with phytohemagglutinin (PHA) and interleukin-2 (IL-2), and
`lipopolysaccharide, respectively. B-LCLs were obtained by Epstein-Barr
`virus (EBV)-transformed PBMCs. MBP-T cell lines were derived from
`PBMCs and expanded in vitro upon several cycles of antigen stimulation.
`gp145trkB protein expression was assessed by western blotting and chemi-
`luminescence assay and related mRNA tested by RT-PCR. To assess the role
`of BDNF signalling in T cell survival, we analyzed apoptosis in anti-CD3 an-
`tibody-stimulated MBP-T cells, in the presence of a neutralizing anti-BDNF
`antibody and K252a, a gp145trkB inhibitor, by annexin V labeling and fluo-
`rescence microscopy.
`Results: gp145trkB was expressed by 5 of 34 (15 %) PHA- and IL-2-stim-
`ulated CD3 + T cell cultures from RRMS patients. No gp145trkB protein ex-
`pression was found in monocytes and in T cells from SPMS patients and HS;
`by contrast, all EBV + B-LCLs and 6 of 9 (67 %) MBP-T cell lines expressed
`gp145trkB. In anti-CD3-stimulated MBP-T cell lines expressing high affinity
`full-length BDNF receptor, apoptosis increased by 42 % (p = 0.03) in the
`presence of the neutralizing anti-BDNF antibody and by 66 % (p = 0.002)
`with K252a.
`Conclusions: gp145trkB protein expression is a cell-specific and activa-
`tion-induced process in inflammatory cells in MS. gp145trkB signalling is
`involved in modulation of peripheral MBP-sensitized T cell line apoptosis,
`suggesting a regulatory role of T cell line survival.
`This work was supported by a grant of the University of Siena to P. A.
`
`O107
`Detection of cortical lesions is dependent on choice of slice thickness in pa-
`tients with multiple sclerosis
`O. Dolezal, S. Balachandran, Z. Seidl, M. Vaneckova, C. I. Tekwe, N. Bergsland,
`M. G. Dwyer, R. Zivadinov
`Buffalo Neuroimaging Analysis Center (Buffalo, USA)
`
`Background: Understanding of the importance of cortical lesions in MS
`pathogenesis has changed. Histopathological studies using new immuno-
`histochemical methods show cortical lesions can be detected more fre-
`quently. Newer MRI sequences also detect cortical lesions more accurately.
`Objective: To evaluate whether the effect of slice thickness (th) is an im-
`portant factor for detection of cortical lesions in patients with multiple scle-
`rosis (MS).
`Design/Methods: 41 patients with relapsing remitting (RR) MS (11
`males,30 females with mean EDSS 2.3) received FLAIR and 3D-T1-WI of 1.5,
`3 and 5 mm slice thickness on 1.5T MRI. Cortical and juxtacortical lesions
`were volumetrically assessed using a semiautomated method. FLAIR and
`3D-T1-WI were co-registered and the matrix of the peripheral gray matter
`(PGM) segmentation mask (SIENAX-generated) classified the location of
`the cortical-subcortical lesions. Cortical lesions fell into three classes. Class
`1 were defined as lesions located in the PGM, Class 2 as juxtacortical lesions
`in contact with PGM mask, and Class 3 as cortical-juxtacortical situated in
`both areas.
`Results: Of total T2-lesion volume (LV) measured on 1.5 mm th scans,
`(mean 16108 cu mm), cortical lesions represented 2.4 % (276 cu mm), juxta-
`
`II/27
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`cortical lesions 6.1 % (760 cu mm) and cortical-juxtacortical 3.7 %. (491 cu
`mm). Compared to 1.5 mm th scans, cortical LV was reduced –28.3 %,
`p < 0.01 on 3 mm th and –40.78 %, p < 0.01on 5 mm th scans. Results for jux-
`tacortical lesions were: (3 mm th scans:–17.9 %,p < 0.01 and –30.3 %,p < 0.01
`for the 5 mm th scans) and (3 mm th scans: –16.22 %, p < 0.01 and –26.7 %,
`p < 0.01 for the 5 mm th scans) for the cortical-juxtacortical lesions.
`Conclusions: Lower slice thickness significantly increases detecting ac-
`curacy of cortical lesions on FLAIR images. Our results support use of
`1.5 mm th for detecting cortical-juxtracortical lesions.
`
`O108
`Efficacy of a novel oral single-agent fumarate, BG00012, in patients with re-
`lapsing-remitting multiple sclerosis: results of a phase 2 study
`L. Kappos, D. H. Miller, D. G. MacManus, R. Gold, E. Havrdova, V. Limmroth,
`C. Polman, K. Schmierer, T.Yousry, M.Yang, M. Eraksoy, E. Meluzinova, I. Rek-
`tor, G. N. O’Neill
`Universitätsspital Basel (Basel, CH); University College London (London,
`UK); University Gottingen and Gemeinnützige Hertie-Stiftung (Gottingen,
`D); General Teaching Hospital (Prague, CZ); City Hospital of Cologne
`(Cologne, D); VU Medical Centre (Amsterdam, NL); Biogen Idec (Cam-
`bridge, USA); University of Istanbul (Istanbul, TR); Faculty Hospital V Mo-
`tole (Prague, CZ); Masaryk University (Brno, CZ)
`
`Objective: To determine the efficacy of three dose levels of BG00012, a novel
`oral fumarate preparation, on brain lesion activity as measured by magnetic
`resonance imaging (MRI) in patients with relapsing-remitting multiple scle-
`rosis (RRMS).
`Methods: This was a randomised, double-blind, placebo-controlled clin-
`ical trial of BG00012 in patients with RRMS. Men and women 18 to 55 years
`of age were eligible for the study if they had a diagnosis of RRMS and an Ex-
`panded Disability Status Scale (EDSS) score between 0.0 and 5.0.In addition,
`patients must have had either ≥ 1 relapse within 12 months prior to ran-
`domisation or gadolinium-enhancing (Gd +) lesions on cranial MRI at
`screening. Patients were assigned to four treatment groups and received
`BG00012 capsules 120 mg by mouth (PO) once daily (120 mg/day), 120 mg
`three times daily (360 mg/day), 240 mg three times daily (720 mg/day), or
`placebo for 24 weeks. The treatment period was followed by a 24-week dose-
`blinded safety-extension period during which all patients received BG00012.
`The primary end point was the total number of Gd + lesions over four MRI
`scans at weeks 12, 16, 20, and 24 (calculated as the sum of the four scans).
`Secondary end points included the cumulative number of new Gd + lesions
`from week 4 to week 24 and the number of new/enlarging T2-hyperintense
`lesions at week 24.Additional end points included the number of new T1-hy-
`pointense lesions at week 24, relapse rate, and disability progression as mea-
`sured by EDSS.
`Results: A total of 257 patients were enrolled in the study; 64 patients
`each were randomly assigned to receive one of the three BG00012 doses and
`65 patients to placebo. Approximately 90 % of patients completed the 24-
`week treatment period. BG00012 (720 mg/day) significantly reduced the
`mean number of new Gd + lesions (the primary end point) compared with
`placebo. In addition, BG00012 reduced the cumulative number of new
`Gd + lesions, the number of new/enlarging T2-hyperintense lesions, and the
`number of new T1-hypointense lesions compared with placebo.
`Conclusion: BG00012 significantly reduces brain lesion activity, in a
`dose-dependent manner, as measured by MRI in patients with RRMS over
`24 weeks of treatment.
`This study was sponsored by Biogen Idec and Fumapharm AG.
`
`O109
`Phase I/II trial of a MBP encoding DNA plasmid (BHT-3009) alone or com-
`bined with atorvastatin for treatment of multiple sclerosis
`H. Garren, J. Antel, A. Bar-Or, C. Bodner, D. Campagnolo, J. Gianettoni, F.
`Jalili, N. Kachuck, Y. Lapierre, M. Niino, J. Oger, M. Price, S. Rhodes, F. Shi, F.
`Valone, T. Vollmer, L. Weiner, L. Steinman
`Bayhill Therapeutics (Palo Alto, USA); Montreal Neurological Inst. (Mont-
`real, CAN); Barrow Neurological Institute (Phoenix, USA); University of
`Southern California (Los Angeles, USA); University of British Columbia
`(Vancouver, CAN); Stanford University (Stanford, USA)
`
`Objective: To assess safety and immune modulation by BHT-3009 in MS pa-
`tients
`Background: We have previously shown that DNA plasmids induce anti-
`gen-specific immunomodulation in animal models of autoimmune disease.
`We have begun clinical testing of BHT-3009, a DNA plasmid that expresses
`full-length human MBP.
`Design/methods: We are conducting a 30 patient, randomized, double-
`blind, placebo-controlled trial in relapsing MS patients. The primary out-
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