Reduction of inflammation and preservation of neurological function by anti-CD52 therapy in murine experimental autoimmune encephalomyelitis

Michael J Turner; Petti T Pang; Nathalie Chretien; Evis Havari; Michael J LaMorte; Julian Oliver; Nilesh Pande; Elizabeth Masterjohn; Karen Carter; David Reczek; William Brondyk; Bruce L Roberts; Johanne M Kaplan; William M Siders

doi:10.1016/j.jneuroim.2015.05.018

Reduction of inflammation and preservation of neurological function by anti-CD52 therapy in murine experimental autoimmune encephalomyelitis

J Neuroimmunol. 2015 Aug 15:285:4-12. doi: 10.1016/j.jneuroim.2015.05.018. Epub 2015 May 20.

Affiliations

¹ Neuroimmunology Research, Genzyme, a Sanofi company, 49 New York Avenue, Framingham, MA 01701, United States. Electronic address: michael.turner@genzyme.com.
² Neuroimmunology Research, Genzyme, a Sanofi company, 49 New York Avenue, Framingham, MA 01701, United States.
³ Pathology, Genzyme, a Sanofi company, 49 New York Avenue, Framingham, MA 01701, United States.
⁴ Biologics Discovery, Genzyme, a Sanofi company, 49 New York Avenue, Framingham, MA 01701, United States.

PMID: 26198912
DOI: 10.1016/j.jneuroim.2015.05.018

Abstract

Alemtuzumab, a monoclonal antibody directed against human CD52, is used in the treatment of MS. To characterize the impact of anti-CD52 administration, a monoclonal antibody to mouse CD52 (anti-muCD52) was generated and evaluated in EAE mouse models of MS. A single course of anti-muCD52 provided a therapeutic benefit accompanied by a reduction in the frequency of autoreactive T lymphocytes and production of pro-inflammatory cytokines. Examination of the CNS revealed a decrease in infiltrating lymphocytes, demyelination and axonal loss. Electrophysiological assessment showed preservation of axonal conductance in the spinal cord. These findings suggest that anti-CD52 therapy may help preserve CNS integrity.

Keywords: Alemtuzumab; CD52; Experimental autoimmune encephalomyelitis; Mouse; Multiple sclerosis.

MeSH terms

Amino Acid Sequence
Animals
Antibodies, Monoclonal / genetics
Antibodies, Monoclonal / pharmacology
Antibodies, Monoclonal / therapeutic use*
Antigens, CD / immunology*
Antigens, Neoplasm / immunology*
Axons / drug effects
Axons / immunology
Axons / pathology
CD52 Antigen
Demyelinating Diseases / drug therapy*
Demyelinating Diseases / immunology*
Demyelinating Diseases / pathology
Encephalomyelitis, Autoimmune, Experimental / drug therapy*
Encephalomyelitis, Autoimmune, Experimental / immunology*
Encephalomyelitis, Autoimmune, Experimental / pathology
Glycoproteins / antagonists & inhibitors
Glycoproteins / immunology*
Humans
Inflammation / drug therapy
Inflammation / immunology
Inflammation / pathology
Inflammation Mediators / antagonists & inhibitors
Inflammation Mediators / immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular Sequence Data

Substances

Antibodies, Monoclonal
Antigens, CD
Antigens, Neoplasm
CD52 Antigen
CD52 protein, human
Glycoproteins
Inflammation Mediators