Rationale for Peptide and DNA Based Epitope Vaccines for Alzheimer's Disease Immunotherapy
Abstract:Amyloid-beta (Aβ) immunotherapy has received considerable attention as a promising approach for reducing the level of Aβ in the CNS of Alzheimer's disease patients. However, the first Phase II clinical trial, for the immune therapy AN1792, was halted when a subset of those immunized with Aβ42 developed adverse events in the central nervous system. In addition, data from the trial indicated that there was a low percentage of responders and generally low to moderate titers in the patients that received the vaccine. Generated antibodies reduced β-amyloid deposits in the parenchyma of patients' brains, but no reduction in soluble Aβ or significant improvements in cognitive function of patients were observed. These data and data from pre-clinical studies suggest that reduction in the most toxic oligomeric forms of Aβ is important for prevention or slowing down of the progression of cognitive decline, and that vaccination should be started prior to irreversible accumulation of the oligomeric Aβ, at the early stages of AD. Protective immunotherapy requires a development of safe and effective strategy for Aβ immunotherapy. In this review, the rationale for developing epitope vaccines for the treatment of AD will be discussed. We believe that an epitope vaccine will induce an adequate anti-Aβ antibody response in the absence of potentially adverse self T cell-mediated events, making it possible to start immunization at the early stages of AD.
Document Type: Research Article
Publication date: April 1, 2009
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- CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.