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Targeting amyloid precursor protein secretases: Alzheimer's disease and beyond

J Kelly Ganjei1

  • 1RemeGenix, Inc., Rockville, MD 20850, USA. kganjei@corticaneuro.com

Drug News & Perspectives
|December 15, 2010
PubMed

Insights

Alzheimer's disease (AD) drug discovery faces challenges, with over half of clinical trials failing. Multifunctional or dual-pathway drugs targeting the amyloid and tau cascades may offer a more effective therapeutic strategy for AD.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited effective treatments.
  • Over 160 clinical trials for AD have been conducted, with a high failure rate.
  • Current AD drug discovery often focuses on single targets within complex disease pathways.

Purpose of the Study:

  • To review and analyze past and present clinical trials for Alzheimer's disease (AD) drug discovery.
  • To assess trends in AD drug discovery in relation to specific drug mechanisms.
  • To identify potential improvements in therapeutic strategies for AD.

Main Methods:

  • Comprehensive review of over 160 clinical trials for Alzheimer's disease (AD).
  • Analysis of preclinical drug candidates and their mechanisms of action.
  • Evaluation of clinical trial outcomes, including endpoint achievement and progress stagnation.
  • Comparison of clinical results with peer-reviewed scientific opinions.

Main Results:

  • 52% of reviewed Alzheimer's disease (AD) clinical trials failed to meet endpoints or stalled.
  • Current approaches may inadequately regulate the amyloid cascade (including Aβ production) and tau cascade.
  • Lack of cognitive function improvement observed in many trials suggests limitations in current strategies.

Conclusions:

  • Many Alzheimer's disease (AD) drug discovery efforts have been unsuccessful due to insufficient pathway regulation.
  • Multifunctional or dual-pathway drugs show promise for future AD therapeutic investigations.
  • Targeting both amyloid and tau cascades may be crucial for effective Alzheimer's disease (AD) treatment.

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