Format

Send to

Choose Destination
J Alzheimers Dis. 2018 Sep 4. doi: 10.3233/JAD-180619. [Epub ahead of print]

A Precision Medicine Model for Targeted NSAID Therapy in Alzheimer's Disease.

Author information

1
Department of Pharmacology & Neuroscience; Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX, USA.
2
Vermont Genetics Network, University of Vermont, VT, USA.
3
University of Texas MD Anderson Cancer Center, TX, USA.
4
George & Anne Ryan Institute for Neuroscience, University of Rhode Island, RI, USA.
5
Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
6
Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA.
7
Department of Neurosciences, UCSD School of Medicine, La Jolla, CA, USA.
8
VA San Diego Healthcare System, San Diego, CA, USA.

Abstract

BACKGROUND:

To date, the therapeutic paradigm for Alzheimer's disease (AD) focuses 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.

KEYWORDS:

Alzheimer’s disease; bioinformatics; biomarkers; clinical trial; inflammation; precision medicine; proteomics

PMID:
30198872
DOI:
10.3233/JAD-180619

Supplemental Content

Full text links

Icon for IOS Press
Loading ...
Support Center