Abstract
In a seminal report in 1999, Schenk and colleagues demonstrated that vaccination of a mouse model of Alzheimers disease (AD) with amyloid-β1-42 peptide (Aβ1-42) and adjuvant resulted in striking mitigation of AD-like pathology – giving rise to the field of AD immunotherapy. Later studies confirmed this result in other mouse models of AD and additionally showed cognitive improvement after Aβ vaccination. Based on these results, early developmental clinical trials ensued to immunize AD patients with Aβ1-42 plus adjuvant (so-called “active” Aβ immunotherapy; trade name AN-1792; Elan Pharmaceuticals, Dublin, Ireland). However, the phase IIa trial was halted after 6 % of patients developed aseptic meningoencephalitis. Despite occurrence of this adverse event, many individuals demonstrated high serum antibody titres to Aβ and histological evidence of clearance of the hallmark AD pathology, β-amyloid plaques. While raising justifiable safety concerns, these important results nonetheless demonstrated the feasibility of the active Aβ immunotherapy approach. This review focuses on alternative approaches to active Aβ vaccination that are currently in various stages of development – from pre-clinical studies in animal models to current clinical trials. Specifically, the focus is on those strategies that target inflammatory and immune aspects of AD, and can therefore be classified as immunotherapeutic in a broad sense.
Keywords: Alzheimer's disease, vaccination, AN-1792, immune, immunization, inflammation, cytokine
CNS & Neurological Disorders - Drug Targets
Title: Alternative Aβ Immunotherapy Approaches for Alzheimers Disease
Volume: 8 Issue: 2
Author(s): Terrence Town
Affiliation:
Keywords: Alzheimer's disease, vaccination, AN-1792, immune, immunization, inflammation, cytokine
Abstract: In a seminal report in 1999, Schenk and colleagues demonstrated that vaccination of a mouse model of Alzheimers disease (AD) with amyloid-β1-42 peptide (Aβ1-42) and adjuvant resulted in striking mitigation of AD-like pathology – giving rise to the field of AD immunotherapy. Later studies confirmed this result in other mouse models of AD and additionally showed cognitive improvement after Aβ vaccination. Based on these results, early developmental clinical trials ensued to immunize AD patients with Aβ1-42 plus adjuvant (so-called “active” Aβ immunotherapy; trade name AN-1792; Elan Pharmaceuticals, Dublin, Ireland). However, the phase IIa trial was halted after 6 % of patients developed aseptic meningoencephalitis. Despite occurrence of this adverse event, many individuals demonstrated high serum antibody titres to Aβ and histological evidence of clearance of the hallmark AD pathology, β-amyloid plaques. While raising justifiable safety concerns, these important results nonetheless demonstrated the feasibility of the active Aβ immunotherapy approach. This review focuses on alternative approaches to active Aβ vaccination that are currently in various stages of development – from pre-clinical studies in animal models to current clinical trials. Specifically, the focus is on those strategies that target inflammatory and immune aspects of AD, and can therefore be classified as immunotherapeutic in a broad sense.
Export Options
About this article
Cite this article as:
Town Terrence, Alternative Aβ Immunotherapy Approaches for Alzheimers Disease, CNS & Neurological Disorders - Drug Targets 2009; 8 (2) . https://dx.doi.org/10.2174/187152709787847306
DOI https://dx.doi.org/10.2174/187152709787847306 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Structural Requirements of Heparin and Related Molecules to Exert a Multitude of Anti-Inflammatory Activities
Mini-Reviews in Medicinal Chemistry The Role of D<sub>2</sub>-like Dopaminergic Receptor in Dopamine-mediated Modulation of Th17-cells in Multiple Sclerosis
Current Neuropharmacology Monocyte Dependent Regulation of Autoimmune Inflammation
Current Molecular Medicine Neuropeptides as Therapeutic Approach to Autoimmune Diseases
Current Pharmaceutical Design Use of Toll-Like Receptor 3 Agonists Against Respiratory Viral Infections
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Cyclooxygenases in the Central Nervous System: Implications for Treatment of Neurological Disorders
Current Pharmaceutical Design An Update on the Roles of the Complement System in Autoimmune Diseases and the Therapeutic Possibilities of Anti-Complement Agents
Current Drug Therapy Glucocorticoid Analogues: Potential Therapeutic Alternatives for Treating Inflammatory Muscle Diseases
Endocrine, Metabolic & Immune Disorders - Drug Targets Subject Index To Volume 2
Current Nutrition & Food Science Synaptic Activity-Regulated Wnt Signaling in Synaptic Plasticity, Glial Function and Chronic Pain
CNS & Neurological Disorders - Drug Targets The Role of miR-124 in Drosophila Alzheimer's Disease Model by Targeting Delta in Notch Signaling Pathway
Current Molecular Medicine Current Opinion in the Pharmaceutical Management of Irritable and Inflammatory Bowel Diseases: Role of ATP
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Therapeutic Options for the Treatment of 2019-Novel Coronavirus in India: A Review
Coronaviruses Gene Therapy Strategies Towards Immune Tolerance to Treat the Autoimmune Diseases
Current Gene Therapy Gene and Cancer Therapy - Pseudorabies Virus: A Novel Research and Therapeutic Tool?
Current Gene Therapy Central Nervous System Involvement in Pediatric Rheumatic Diseases: Current Concepts in Treatment
Current Pharmaceutical Design The Leptin System: A Potential Target for Sepsis Induced Immune Suppression
Endocrine, Metabolic & Immune Disorders - Drug Targets Classical to Current Approach for Treatment of Psoriasis: A Review
Endocrine, Metabolic & Immune Disorders - Drug Targets Immunologic Modulations to Enhance Post-Stroke Recovery
Current Immunology Reviews (Discontinued) Immunological Approaches to Prevent Neuronal Apoptosis During Neuroinflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents