Nature Medicine
6, 1176 - 1182 (2000)
doi:10.1038/80525
Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response
in multiple sclerosis after administration of an altered peptide ligand in
a placebo-controlled, randomized phase II trialLudwig Kappos1, Giancarlo Comi2, Hillel Panitch3, Joel Oger4, Jack Antel5, Paul Conlon6, Lawrence Steinman7, Giancarlo Comi8, 24, Ludwig Kappos9, 24, Joel Oger10, 24, Hillel Panitch11, 24, Alexander Rae-Grant12, 24, John Castaldo13, 24, Nancy Eckert13, 24, Joseph B. Guarnaccia13, 24, Pamela Mills14, 24, Gary Johnson14, 24, Peter A. Calabresi14, 24, Carlo Pozzilli15, 24, Stefano Bastianello15, 24, Elisabetta Giugni15, 24, Tatiana Witjas16, 24, Patrick Cozzone16, 24, Jean Pelletier16, 24, Dieter Pöhlau17, 24, Horst Przuntek17, 24, Volker Hoffmann17, 24, Christopher Bever Jr11, 24, Eleanor Katz11, 24, Michel Clanet18, 24, Isabelle Berry18, 24, David Brassat18, 24, Irene Brunet19, 24, Gilles Edan19, 24, Pierre Duquette20, 24, Ernst-Wilhelm Radue9, 24, Dagmar Schött9, 24, Carmen Lienert9, 24, Alice Taksaoui9, 24, M. Rodegher8, 24, M. Filippi8, 24, Alan Evans21, 24, Pierre Bourgouin21, 24, Alex Zijdenbos21, 24, Shawki Salem22, 24, Nicholas Ling23, 24, David Alleva23, 24, Eric Johnson23, 24, Amitabh Gaur23, 24, Paul Crowe23, 24
& Xin-Jun Liu23, 241
Department of Neurology, University Hospitals,
Petersgraben 4, CH-4031, Basel, Switzerland
2
Department of Neuroscience, Scientific Institute H.
, San Raffaele via Olgettina 60, 20132,
Milano, Italy
3
Department of Neurology, Room N4W46, Univ. of Maryland
School of Medicine, Baltimore Maryland, 21201,
USA
4
Division of Neurology, Univ. of British Columbia,
211 Westbrook Mall, Vancouver, V6T 2B5,
Canada
5
Department of Neurology & Neurosurgery, McGill
University, Neuroimmunology Unit, Montreal Neurological Institute, McGill
University, Montreal, Quebec, H3A 2B4,
Canada
6
Neurocrine Biosciences, 10555 Science
Center Drive, San Diego, California, 92121
, USA
7
Department of Neurology/Neuroscience, Beckman Center
B002, Stanford Univ. School of Medicine, Stanford, California
94305, USA
8
Department of Neuroscience, Scientific Institute H
San Raffaele, via Olgettina, Milano, Italy
9
Department of Neurology, University Hospitals,
Petersgraben 4, Basel, Switzerland
10
Vancouver, Canada
11
Department of Neurology, Room N4W46, Univ. of Maryland
School of Medicine, Baltimore Maryland, 21201,
USA
12
Leigh Valley Hospital, 1210 Cedar Crest
Blvd. Allentown, Pennsylvania, 18103
13
Yale MS Clinic, 40 Temple St.
New Haven, Connecticut, 06510, USA
14
Brown University School of Medicine, Rhode Island
Hospital, Providence, Rhode Island, 02903,
USA
15
Department of Neurological Science, University of
Rome 'La Sapienza', Rome, Italy
16
CHU Timone, Marseille, France
17
Ruhr-Universität Bochum, St.Josef-Hospital, Neurologische
Klinik, Bochum, Germany
18
Service de Neurologie, CHU Toulouse,
France
19
Clinique Neurologique CHU Pontchaillou,
Rennes, France
20
Neurology Dept. Université de Montréal,
Montréal, General Hosp, Montréal PO,
Canada, H2M 2L7
21
McConnell Brain Imaging Centre of the Montreal Neurological
Institute, Montreal PO Canada, CA H3A 2B4
22
Symbiance, 12 Banff Dr. Princeton,
New Jersey, 08550 USA
23
Neurocrine Biosciences, 10555 Science
Center Drive, San Diego, California, 92121
, USA
24
The Atlered peptide ligand in Relapsing MS Study Group
Correspondence should be addressed to Lawrence Steinman steinman@stanford.eduIn this 'double-blind', randomized, placebo-controlled phase
II trial, we compared an altered peptide ligand of myelin basic protein with
placebo, evaluating their safety and influence on magnetic resonance imaging
in relapsing−remitting multiple sclerosis. A safety board suspended
the trial because of hypersensitivity reactions in 9% of the patients. There
were no increases in either clinical relapses or in new enhancing lesions
in any patient, even those with hypersensitivity reactions. Secondary analysis
of those patients completing the study showed that the volume and number of
enhancing lesions were reduced at a dose of 5 mg. There was also a regulatory
type 2 T helper-cell response to altered peptide ligand that cross-reacted
with the native peptide.
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