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Lost in Translation? Finding Our Way To Effective Alzheimer's Disease Therapies
1Oregon Health and Science University, Portland VA Medical Center, Department of Neurology, Portland, OR, USA.
Abstract:
Efforts over the past two decades to develop effective disease-modifying treatments for Alzheimer's disease have been disappointing, while parallel efforts in another chronic neurologic disease, multiple sclerosis, have been remarkably productive. In an effort to advance development of therapeutics for Alzheimer's disease, these two fields are contrasted in terms of the utility of animal models, definition of study populations, and utility of biomarkers. Possible solutions are suggested, and the review concludes with description of some active peer-reviewed, publicly funded clinical studies which address some of the identified weaknesses in past clinical trials for age-related dementia.
Insights
Developing Alzheimer's disease treatments lags behind multiple sclerosis due to issues with animal models, patient selection, and biomarkers. This review contrasts the fields and suggests improvements for future clinical trials in dementia research.
Area of Science:
- Neurology
- Neurodegenerative Diseases
- Clinical Trial Design
Background:
- Alzheimer's disease (AD) therapeutic development has yielded disappointing results over two decades.
- In contrast, multiple sclerosis (MS) research has seen productive advancements in disease-modifying treatments.
- This disparity highlights critical differences in research approaches.
Purpose of the Study:
- To contrast AD and MS research fields to identify reasons for differing therapeutic success.
- To analyze the utility of animal models, study population definitions, and biomarkers in AD drug development.
- To propose solutions and highlight promising clinical trials for age-related dementia.
Main Methods:
- Comparative analysis of research methodologies in Alzheimer's disease and multiple sclerosis.
- Review of existing literature on animal models, patient stratification, and biomarker utility in neurodegenerative disease research.
- Identification and description of ongoing, publicly funded clinical studies for dementia.
Main Results:
- Significant differences exist in the predictive validity of animal models between AD and MS.
- Challenges in defining homogenous study populations and utilizing reliable biomarkers impede AD clinical trial success.
- Current AD trials may not adequately address the complexities of the disease pathology.
Conclusions:
- Improving animal models, refining patient selection criteria, and validating robust biomarkers are crucial for advancing AD therapeutics.
- Learning from the productive MS research field can offer valuable insights for AD drug development.
- Active clinical studies are beginning to address identified weaknesses in past AD trials.