PrP antibodies do not trigger mouse hippocampal neuron apoptosis.
Intraperitoneal administration of ICSM18 and 35, monoclonal antibodies against prion protein (PrP), has been shown to significantly delay the onset of prion disease in mice, and humanized versions are candidate therapeutics for prion and Alzheimer's diseases. However, a previous report of severe and widespread apoptosis after intracerebral injection of anti-PrP monoclonal antibodies raised concerns about such therapy and led to an influential model of prion neurotoxicity via cross-linking of cell surface PrP by disease-related PrP aggregates. In extensive studies including ICSM18 and 35, fully humanized ICSM18, and the previously reported proapoptotic antibodies, we found no evidence of apoptosis, thereby questioning this model of prion neurotoxicity.
Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, University College London Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Peter-Christian
PC
Klöhn
Michael
M
Farmer
Jacqueline M
JM
Linehan
Catherine
C
O'Malley
Mar
M
Fernandez de Marco
William
W
Taylor
Mark
M
Farrow
Azy
A
Khalili-Shirazi
Sebastian
S
Brandner
John
J
Collinge
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000276:immunology; D017209:Apoptosis; D000939:Epitopes / Q000276:immunology; D006624:Hippocampus / Q000166:cytology*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000276:immunology / Q000502:physiology*; D018621:PrPC Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000939:Epitopes; D007074:Immunoglobulin G; D018621:PrPC Proteins