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A Precision Medicine Model for Targeted NSAID Therapy in Alzheimer's Disease
Sid E O'Bryant1, Fan Zhang2, Leigh A Johnson1
1Department of Pharmacology & Neuroscience; Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX, USA.
Background:
To date, the therapeutic paradigm for Alzheimer's disease (AD) has focused on a single intervention for all patients. However, a large literature in oncology supports the therapeutic benefits of a precision medicine approach to therapy. Here we test a precision-medicine approach to AD therapy.
Objective:
To determine if a baseline, blood-based proteomic companion diagnostic predicts response to NSAID therapy.
Methods:
Proteomic assays of plasma from a multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to rofecoxib (25 mg once daily), naproxen (220 mg twice-daily) or placebo.
Results:
474 participants with mild-to-moderate AD were screened with 351 enrolled into the trial. Using support vector machine (SVM) analyses, 89% of the subjects randomized to either NSAID treatment arms were correctly classified using a general NSAID companion diagnostic. Drug-specific companion diagnostics yielded 98% theragnostic accuracy in the rofecoxib arm and 97% accuracy in the naproxen arm.
Conclusion:
Inflammatory-based companion diagnostics have significant potential to identify select patients with AD who have a high likelihood of responding to NSAID therapy. This work provides empirical support for a precision medicine model approach to treating AD.
Insights
A new blood test can identify Alzheimer's disease (AD) patients likely to respond to non-steroidal anti-inflammatory drugs (NSAIDs). This precision medicine approach shows high accuracy in predicting treatment success for AD.
Area of Science:
- Neuroscience
- Pharmacology
- Biomarkers
Background:
- Current Alzheimer's disease (AD) treatment lacks personalization.
- Precision medicine, successful in oncology, offers a potential alternative for AD therapy.
Purpose of the Study:
- To evaluate a blood-based proteomic companion diagnostic for predicting response to NSAID therapy in AD patients.
Main Methods:
- Plasma proteomic assays were conducted on participants in a randomized, double-blind, placebo-controlled trial.
- Participants received rofecoxib, naproxen, or placebo for one year.
- Support vector machine (SVM) analysis was used to develop companion diagnostics.
Main Results:
- A general NSAID companion diagnostic correctly classified 89% of patients responding to NSAID treatment.
- Drug-specific companion diagnostics achieved 98% accuracy for rofecoxib and 97% for naproxen.
Conclusions:
- Inflammatory-based companion diagnostics can identify AD patients likely to benefit from NSAID therapy.
- This study supports a precision medicine model for treating Alzheimer's disease.