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Resolving controversies on the path to Alzheimer's therapeutics

Dennis J Selkoe1

  • 1Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Nature Medicine
|September 9, 2011
PubMed

Insights

Despite setbacks, Alzheimer's disease research is advancing. Future success in treating Alzheimer's disease (AD) hinges on rigorous preclinical validation and trials targeting early cognitive symptoms and biomarkers.

Area of Science:

  • Neuroscience
  • Clinical Research
  • Pharmacology

Background:

  • Alzheimer's disease (AD) is a devastating neurodegenerative syndrome with significant personal and societal impact.
  • Decades of research have advanced understanding of AD, leading to initial therapeutic trials.
  • Recent clinical trial failures and knowledge gaps raise concerns about AD research progress.

Purpose of the Study:

  • To address concerns and knowledge gaps in Alzheimer's disease research.
  • To offer explanations for recent therapeutic trial failures in AD.
  • To propose a path forward for successful Alzheimer's disease treatment development.

Main Methods:

  • Review and analysis of existing Alzheimer's disease research and clinical trial data.
  • Discussion of preclinical validation strategies for therapeutic agents.
  • Examination of trial design considerations, including patient population and outcome measures.

Main Results:

  • Identified potential reasons for the failure of some disease-modifying agents in AD clinical trials.
  • Highlighted the importance of rigorous preclinical validation for mechanism-based therapeutic agents.
  • Emphasized the need for meticulously designed trials focusing on early disease stages.

Conclusions:

  • Recent Alzheimer's disease trial failures are not necessarily predictive of future outcomes.
  • Success in treating Alzheimer's disease may be achieved through rigorous preclinical work and well-designed clinical trials.
  • Future therapeutic strategies should focus on mild or presymptomatic Alzheimer's disease, targeting cognitive symptoms and biomarkers.

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