Blockade of chemokine signaling in patients with multiple sclerosis.
We assessed the safety and efficacy of orally administered CC chemokine receptor 1 (CCR1) antagonist in 105 patients with relapsing/remitting MS (RRMS) in a 16-week, randomized, double-blind, placebo-controlled trial. The primary endpoint was the cumulative number of newly active lesions on serial MRI scans. Other MRI, immunologic, and clinical outcomes were also explored. No significant treatment difference was observed for any tested MRI variable. CCR1 does not contribute to initial leukocyte infiltration in RRMS.
Zipp
F
F
Institute of Neuroimmunology, Neuroscience Research Center, NWFZ 2680, Charité, 10098 Berlin, Germany. frauke.zipp@charite.de
Hartung
H P
HP
Hillert
J
J
Schimrigk
S
S
Trebst
C
C
Stangel
M
M
Infante-Duarte
C
C
Jakobs
P
P
Wolf
C
C
Sandbrink
R
R
Pohl
C
C
Filippi
M
M
D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018925:Chemokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008279:Magnetic Resonance Imaging; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D010919:Placebos; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
C515300:CCR1 protein, human; D018925:Chemokines; D007166:Immunosuppressive Agents; D010671:Phenylurea Compounds; D010880:Piperidines; D010919:Placebos; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; C411885:BX 471