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

Bert A 't Hart; Erwin L A Blezer; Herbert P M Brok; Louis Boon; Mark de Boer; Jan Bauer; Jon D Laman

doi:10.1016/j.jneuroim.2005.02.005

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

J Neuroimmunol. 2005 Jun;163(1-2):31-9. doi: 10.1016/j.jneuroim.2005.02.005. Epub 2005 Apr 9.

Authors

Bert A 't Hart¹, Erwin L A Blezer, Herbert P M Brok, Louis Boon, Mark de Boer, Jan Bauer, Jon D Laman

Affiliation

¹ Department of Immunobiology, Biomedical Primate Research Center, Rijswijk, The Netherlands. [email protected]

PMID: 15885306
DOI: 10.1016/j.jneuroim.2005.02.005

Abstract

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / administration & dosage
Anti-Inflammatory Agents / therapeutic use
Autoantibodies / administration & dosage*
Autoantibodies / genetics
Autoantibodies / therapeutic use*
Brain / drug effects*
Brain / immunology
CD40 Antigens / immunology*
Callithrix
Encephalomyelitis, Autoimmune, Experimental / immunology*
Encephalomyelitis, Autoimmune, Experimental / pathology*
Encephalomyelitis, Autoimmune, Experimental / prevention & control*
Immunosuppressive Agents / administration & dosage
Immunosuppressive Agents / therapeutic use*
Magnetic Resonance Imaging* / methods
Male
Myelin Proteins
Myelin-Associated Glycoprotein* / toxicity
Myelin-Oligodendrocyte Glycoprotein
Recombinant Fusion Proteins / administration & dosage
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / therapeutic use*

Substances

Anti-Inflammatory Agents
Autoantibodies
CD40 Antigens
Immunosuppressive Agents
MOG protein, human
Myelin Proteins
Myelin-Associated Glycoprotein
Myelin-Oligodendrocyte Glycoprotein
Recombinant Fusion Proteins