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Published on: May 28, 2017
Alzheimer Disease Clinical Trials Targeting Amyloid: Lessons Learned From Success in Mice and Failure in Humans
Allison B Reiss1, Natalie Montufar1, Joshua DeLeon1
1Department of Medicine, NYU Long Island School of Medicine, Mineola, NY.
Background:
The goal of slowing or halting the development of Alzheimer disease (AD) has resulted in the huge allocation of resources by academic institutions and pharmaceutical companies to the development of new treatments. The etiology of AD is elusive, but the aggregation of amyloid-β and tau peptide and oxidative processes are considered critical pathologic mechanisms. The failure of drugs with multiple mechanisms to meet efficacy outcomes has caused several companies to decide not to pursue further AD studies and has left the field essentially where it has been for the past 15 years. Efforts are underway to develop biomarkers for detection and monitoring of AD using genetic, imaging, and biochemical technology, but this is of minimal use if no intervention can be offered.
Review Summary:
In this review, we consider the natural progression of AD and how it continues despite present attempts to modify the amyloid-related machinery to alter the disease trajectory. We describe the mechanisms and approaches to AD treatment targeting amyloid, including both passive and active immunotherapy as well as inhibitors of enzymes in the amyloidogenic pathway.
Conclusion:
Lessons learned from clinical trials of amyloid reduction strategies may prove crucial for the leap forward toward novel therapeutic targets to treat AD.
Insights
Despite extensive research, Alzheimer disease (AD) treatments targeting amyloid have shown limited success. Lessons learned from these trials are vital for developing effective future Alzheimer disease interventions.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Alzheimer disease (AD) research has heavily invested in treatments targeting amyloid-β and tau.
- The complex etiology of AD, involving oxidative stress, remains elusive.
- Previous drug development failures highlight the need for novel therapeutic strategies.
Purpose of the Study:
- To review the natural progression of Alzheimer disease.
- To analyze current amyloid-targeting treatment mechanisms and approaches.
- To identify key lessons from clinical trials for future AD therapy development.
Main Methods:
- Literature review of Alzheimer disease progression.
- Analysis of amyloid-targeting therapeutic strategies, including immunotherapy and enzyme inhibitors.
- Evaluation of clinical trial outcomes for amyloid reduction methods.
Main Results:
- Alzheimer disease progression persists despite interventions targeting amyloid.
- Review details passive and active immunotherapies and amyloidogenic pathway inhibitors.
- Current amyloid-focused strategies have not significantly altered disease trajectory.
Conclusions:
- Clinical trials of amyloid reduction strategies offer critical insights.
- Lessons learned are essential for advancing novel therapeutic targets for Alzheimer disease.
- Future research must leverage past findings to develop more effective AD treatments.
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