Changing the Course of Alzheimers Disease: Emerging Disease Modifying Therapies

Author(s): Daniel D. Christensen.

Journal Name: Current Psychiatry Reviews

Volume 2 , Issue 2 , 2006

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Abstract:

Drugs that prevent the onset, delay the progression, or eliminate the symptoms of Alzheimers disease are urgently needed. Current neurotransmitter-based treatments are widely used and provide modest symptom relief. The amyloid hypothesis in which the pathological processing of amyloid precursor protein (APP) produces the toxic 42-amino acid peptide (i.e., Aβ42) and initiates a cascade of amyloid accumulation, neurodegeneration, plaque formation, and dementia, is the predominant mechanistic theory of Alzheimers disease. Drug development programs focus on Aβ42, the enzymes involved in its generation (i.e., γ-secretase, β-secretase), APP, Aβ aggregation, and plaque formation as targets for therapeutic intervention. Disease modifying drugs being studied include anti-amyloid immunotherapy (active and passive immunization), γ-secretase inhibitors (LY450139), β-secretase inhibitors, selective A β42 lowering agents (Flurizan ), inhibitors of amyloid aggregation (Alzhemed™), and others. Preclinical studies and clinical trials suggest that drugs with anti-amyloid properties produce cognitive benefit. However, tolerability and adverse events are important factors to consider when developing treatments for the elderly. Disease modifying drugs that specifically target the amyloid cascade and do not interact with other biological pathways are expected to possess a lower rate of unintended adverse events. Discovery of safe and effective disease modifying therapies will usher in a new age of Alzheimers disease treatment.

Keywords: Alzheimer's disease, amyloid, disease-modifying

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Article Details

VOLUME: 2
ISSUE: 2
Year: 2006
Page: [179 - 188]
Pages: 10
DOI: 10.2174/157340006776875978
Price: $58

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