Claude Paul Genain, M.D.
Email: GenainC@cpmcri.org
Introduction
My research program focuses on understanding the pathological processes involved in human multiple sclerosis (MS), and on the development of novel therapeutic approaches to this disease. My laboratory has developed a sophisticated model of experimental allergic encephalomyelitis (EAE) in a small outbred New World primate, the common marmoset Callithrix jacchus (C. jacchus), which is highly reminiscent of human MS. The MS-like, primary demyelinating lesion in C. jacchus results from a complex immune response directed against several myelin antigens. While myelinreactive T-cells are capable of mediating the inflammatory component, the presence of pathogenic antibody responses is required for demyelination. An important target for these antibodies is myelin oligodendrocyte glycoprotein (MOG), a surface-expressed protein of myelin. Autoantibodies specific for MOG have been directly identified in situ in contact with disintegrating myelin sheaths within areas of ongoing demyelination, not only in marmoset EAE, but also in lesions in human MS.
We are investigating the mechanisms by which these autoantibodies promote demyelination. Preliminary experiments indicate that intact antibody is required, as opposed to F(ab)2 fragments, suggesting that pathogenicity is dependent upon functions supported by Fc fragments, for example complement or macrophage activation. It is possible to prevent demyelination in C. jacchus by administration of MOG-specific F(ab)2 fragments that competitively block the effect of the intact antibodies.
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Publications
Click here for List of publications by Claude P Genain, M.D. in PubMed.
Recent publications include:
1: Menge T, von Büdingen HC, Lalive PH, Genain CP. Relevant antibody subsets against MOG recognize conformational epitopes exclusively exposed in solid-phase ELISA.
Eur J Immunol. 2007 Nov;37(11):3229-39.
2: Gardell JL, Dazin P, Islar J, Menge T, Genain CP, Lalive PH. Apoptotic effects of Human Herpesvirus-6A on glia and neurons as potential triggers for central nervous system autoimmunity.
J Clin Virol. 2006 Dec;37 Suppl 1:S11-6.
3: Lalive PH, Menge T, Barman I, Cree BA, Genain CP. Identification of new serum autoantibodies in neuromyelitis optica using protein microarrays.
Neurology. 2006 Jul 11;67(1):176-7.
4: Lalive PH, Menge T, Delarasse C, Della Gaspera B, Pham-Dinh D, Villoslada P, von Büdingen HC, Genain CP. Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis.
Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2280-5. Epub 2006 Feb 3.
5: Menge T, Lalive PH, von Büdingen HC, Cree B, Hauser SL, Genain CP. Antibody responses against galactocerebroside are potential stage-specific biomarkers in multiple sclerosis.
J Allergy Clin Immunol. 2005 Aug;116(2):453-9.
6: Kauppinen TM, Suh SW, Genain CP, Swanson RA. Poly(ADP-ribose) polymerase-1 activation in a primate model of multiple sclerosis.
J Neurosci Res. 2005 Jul 15;81(2):190-8.
7: Cree BA, Lamb S, Morgan K, Chen A, Waubant E, Genain C. An open label study of the effects of rituximab in neuromyelitis optica.
Neurology. 2005 Apr 12;64(7):1270-2.
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