Treatment with chimeric anti-human CD40 antibody suppresses MRI-detectable inflammation and enlargement of pre-existing brain lesions in common marmosets affected by MOG-induced EAE.
Common marmosets, a Neotropical monkey species, are protected against clinical and neuropathological consequences of experimentally induced autoimmune encephalomyelitis (EAE) by prophylactic treatment with ch5D12, a humanized antagonist antibody against human CD40. In the current study we have tested whether ch5D12 acts therapeutically against the enlargement and inflammatory activity of existing (brain) white matter lesions using serial magnetic resonance imaging (MRI). The results show in all PBS treated monkeys (n=4) a rapid enlargement of T2 lesions together with an increment of the T2 signal intensity due to inflammatory edema. Treatment with ch5D12 delayed the enlargement of T2 lesions in 2 out of 3 tested monkeys while in 3 out of 3 monkeys the T2 signal increment of lesions was suppressed. In conjunction with previously published data on the clinical benefit of anti-CD40 treatment in the marmoset EAE model, the current findings support antibody-mediated blockade of CD40 interaction with its ligand CD154 as a potential treatment of MS.
't Hart
Bert A
BA
Department of Immunobiology, Biomedical Primate Research Center, Rijswijk, The Netherlands. hart@bprc.nl
Blezer
Erwin L A
EL
Brok
Herbert P M
HP
Boon
Louis
L
de Boer
Mark
M
Bauer
Jan
J
Laman
Jon D
JD
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001323:Autoantibodies / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D002144:Callithrix; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000633:toxicity; D063308:Myelin-Oligodendrocyte Glycoprotein; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D001323:Autoantibodies; D019013:CD40 Antigens; D007166:Immunosuppressive Agents; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D011993:Recombinant Fusion Proteins