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

Sid E. O'Bryant, Fan Zhang, Leigh A. Johnson, James Hall, Melissa Edwards, Paula Grammas, Esther Oh, Constantine G. Lyketsos, Robert A. Rissman

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)97-104
Number of pages8
JournalJournal of Alzheimer's disease : JAD
Volume66
Issue number1
DOIs
StatePublished - 2018

Keywords

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

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