Clinical Trials of Intravenous Immunoglobulin for Alzheimer's Disease

被引:54
作者
Relkin, Norman [1 ,2 ]
机构
[1] Weill Cornell Med Coll, Dept Neurol, New York, NY 10065 USA
[2] Weill Cornell Med Coll, Brain Mind Res Inst, New York, NY USA
关键词
Human intravenous immunoglobulin; polyclonal IgG; alzheimer's disease; beta amyloid; immunotherapy; clinical trials; AMYLOID-BETA-PEPTIDE; HUMAN-ANTIBODIES; PATHOLOGY;
D O I
10.1007/s10875-014-0041-4
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The human polyclonal IgG antibody preparation known as Intravenous Immunoglobulin (IVIG) has been under study as a potential treatment for Alzheimer's disease (AD) since 2002. Preclinical and clinical studies have shown that IVIG has anti-amyloid and immune modulatory properties relevant to treating neurodegenerative disorders. In early stage AD clinical trials, IVIG was found to reduce cognitive decline and increase brain glucose metabolism. Unfortunately, IVIG failed to meet primary outcome objectives in the North American Phase 3 clinical trial in mild to moderate AD. However, positive cognitive signals were observed in pre-planned subgroup analyses among APOE-epsilon 4 carriers and moderately impaired AD patients. Biomarker studies revealed dose dependent increases in plasma and CSF immunoglobulins and decreases in beta amyloid-42 levels. In addition, IVIG treatment was generally safe and well-tolerated. These findings suggest that naturally occurring human anti-amyloid antibodies may play a physiologic role in the clearance of aggregated amyloid proteins. While the results of clinical trials to date do not provide support for the use of IVIG to treat AD at the doses tested, additional studies of IVIG's mechanisms are warranted and may guide the development of more effective therapies for AD in the future.
引用
收藏
页码:S74 / S79
页数:6
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