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Targeting Beta amyloid: a clinical review of immunotherapeutic approaches in Alzheimer's disease.

ABSTRACT: As the societal and economic burdens of Alzheimer's disease (AD) continue to mount, so does the need for therapies that slow the progression of the illness. Beta amyloid has long been recognized as the pathologic hallmark of AD, and the past decade has seen significant progress in the development of various immunotherapeutic approaches targeting beta amyloid. This paper reviews active and passive approaches aimed at beta amyloid, with a focus on clinical trial data.

SUBMITTER: Lobello K

PROVIDER: S-EPMC3265072 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Targeting Beta amyloid: a clinical review of immunotherapeutic approaches in Alzheimer's disease.

Lobello Kasia K Ryan J Michael JM Liu Enchi E Rippon Gregory G Black Ronald R

International journal of Alzheimer's disease 20120115

As the societal and economic burdens of Alzheimer's disease (AD) continue to mount, so does the need for therapies that slow the progression of the illness. Beta amyloid has long been recognized as the pathologic hallmark of AD, and the past decade has seen significant progress in the development of various immunotherapeutic approaches targeting beta amyloid. This paper reviews active and passive approaches aimed at beta amyloid, with a focus on clinical trial data. ...[more]

PMID: 22292124

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Project description:Alzheimer's disease (AD) is an age-related neurodegenerative disease that affects 50 million people worldwide, with 10 million new cases occurring each year. The emotional and economic impacts of AD on patients and families are devastating. Approved treatments confer modest improvement in symptoms, and recently one treatment obtained accelerated approval from the United States Food and Drug Administration (FDA) and may have modest disease modifying benefit. Research over the past three decades has established a clear causal linkage between AD and elevated brain levels of amyloid β (Aβ) peptide, and substantial evidence now implicates soluble, non-fibrillar Aβ oligomers (AβOs) as the molecular assemblies directly responsible for AD-associated memory and cognitive failure and accompanying progressive neurodegeneration. The widely recognized linkage of elevated Aβ and AD spawned a comprehensive 20-year therapeutic campaign that focused primarily on two strategies - inhibition of the secretase enzymes responsible for Aβ production and clearance of Aβ peptide or amyloid plaques with Aβ-directed immunotherapeutics. Unfortunately, all clinical trials of secretase inhibitors were unsuccessful. Of the completed phase 3 immunotherapy programs, bapineuzumab (targeting amyloid plaque) and solanezumab (targeting Aβ monomers) were negative, and the crenezumab program (targeting Aβ monomers and to a small extent oligomers) was stopped for futility. Aducanumab (targeting amyloid plaques), which recently received FDA accelerated approval, had one positive and one negative phase 3 trial. More than 25 negative randomized clinical trials (RCTs) have evaluated Aβ-targeting therapeutics, yet none has directly evaluated whether selective blockage of disease-relevant AβOs can stop or reverse AD-associated cognitive decline. Here, we briefly summarize studies that establish the AD therapeutic rationale to target AβOs selectively, and we describe ACU193, the first AβO-selective immunotherapeutic to enter human clinical trials and the first positioned to test the AβO hypothesis of AD.

Dataset Information

Targeting Beta amyloid: a clinical review of immunotherapeutic approaches in Alzheimer's disease.

Publications

Targeting Beta amyloid: a clinical review of immunotherapeutic approaches in Alzheimer's disease.

Similar Datasets

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