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 sever...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2012-01, Vol.335 (6064), p.52-52
Main Authors: Klöhn, Peter-Christian, Farmer, Michael, Linehan, Jacqueline M., O'Malley, Catherine, de Marco, Mar Fernandez, Taylor, William, Farrow, Mark, Khalili-Shirazi, Azy, Brandner, Sebastian, Collinge, John
Format: Article
Language:English
Subjects:
Alzheimer's disease
Animals
Antibodies
Antibodies, Monoclonal - administration & dosage
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal, Humanized - administration & dosage
Antibodies, Monoclonal, Humanized - immunology
Apoptosis
Biological and medical sciences
Brain
BREVIA
Epitopes - immunology
Fundamental and applied biological sciences. Psychology
Hemorrhage
Hippocampus
Hippocampus - cytology
Immunoglobulin G - administration & dosage
Immunoglobulin G - immunology
Immunoglobulins
Injection sites
Isotypes
Medical treatment
Mice
Mice, Inbred C57BL
Monoclonal antibodies
Neurons
Neurons - immunology
Neurons - physiology
Prions
PrPC Proteins - immunology
Rodents
Vertebrates: nervous system and sense organs
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1215579