Active and passive immunotherapy for neurodegenerative disorders.

Abstract

Immunotherapeutic strategies to combat neurodegenerative disorders have galvanized the scientific community since the first dramatic successes in mouse models recreating aspects of Alzheimer disease (AD) were reported. However, initial human trials of active amyloid-beta (Abeta) vaccination were halted early because of a serious safety issue: meningoencephalitis in 6% of subjects. Nonetheless, some encouraging preliminary data were obtained, and rapid progress has been made toward developing alternative, possibly safer active and passive immunotherapeutic approaches for several neurodegenerative conditions. Many of these are currently in human trials for AD. Despite these advances, our understanding of the essential mechanisms underlying the effects seen in preclinical models and human subjects is still incomplete. Antibody-induced phagocytosis of pathological protein deposits, direct antibody-mediated disruption of aggregates, neutralization of toxic soluble proteins, a shift in equilibrium toward efflux of specific proteins from the brain, cell-mediated immune responses, and other mechanisms may all play roles depending on the specific immunotherapeutic scenario.

• Authors: David L Brody, David M Holtzman
• Journal: Annual review of neuroscience (Annu Rev Neurosci) Vol. 31 Pg. 175-93 ( 2008) ISSN: 0147-006X [Print] United States
• PMID: 18352830 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Amyloid beta-Peptides
• Antibodies
• Nerve Tissue Proteins

Topics

• Amyloid beta-Peptides (immunology)
• Animals
• Antibodies (immunology, metabolism)
• Humans
• Immunity (immunology)
• Immunization, Passive (methods, trends)
• Immunotherapy, Active (methods, trends)
• Nerve Tissue Proteins (immunology, metabolism)
• Neurodegenerative Diseases (immunology, physiopathology, therapy)
• Vaccination (adverse effects)