Treatment with atacicept enhances neuronal cell death in a rat model of optic neuritis.
We investigated the effect of atacicept, a recombinant fusion protein blocking BLyS and APRIL and acting on B cells, on degeneration of retinal ganglion cells (RGCs) during experimental autoimmune encephalomyelitis (EAE). We used myelin oligodendrocyte glycoprotein in Brown Norway rats to induce a variant of EAE which involves B cells and leads to severe optic neuritis. Intraperitoneal treatment with atacicept at some of the studied dose levels (100 or 200 μg) resulted in increased apoptosis of retinal ganglion cells whereas at a tenfold lower dose or in vehicle-treated animals no such effect became apparent. Also the extent of inflammation, demyelination, and axonal loss of the optic nerve was more pronounced in rats treated with the higher atacicept dose level. The present study describes observational evidence for adverse effects of atacicept on neuronal survival during EAE.
Department of Neurology, University Medicine Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany. Electronic address: Benedikt.Kretzschmar@med.uni-goettingen.de.
Benedikt
B
Kretzschmar
Department of Neurology, University Medicine Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
Katharina
K
Hein
Department of Neurology, University Medicine Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
Zahra
Z
Moinfar
Department of Neurology, University Medicine Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
Birte
B
Könnecke
Department of Neurology, University Medicine Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
Muriel B
MB
Sättler
Merck KGaA, Frankfurter Str. 250, 64293 Darmstadt, Germany.
Henry
H
Hess
Merck Serono S.A., Geneva Research Center, 9 Chemin des Mines, 1211 Geneva 20, Switzerland.
Robert
R
Weissert
Department of Neurology, University Medicine Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
Mathias
M
Bähr
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009902:Optic Neuritis / Q000473:pathology*; D051381:Rats; D011914:Rats, Inbred BN; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology
D011993:Recombinant Fusion Proteins; C524618:TACI receptor-IgG Fc fragment fusion protein
APRIL; Atacicept; B cell; BLyS; Experimental autoimmune encephalomyelitis; Optic neuritis