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

Sidney 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 journalArticleResearchpeer-review

1 Citation (Scopus)

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 - 1 Jan 2018

Fingerprint

Precision Medicine
Non-Steroidal Anti-Inflammatory Agents
Alzheimer Disease
Naproxen
Proteomics
Therapeutics
Placebos
Pharmaceutical Preparations

Keywords

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

Cite this

O'Bryant, Sidney ; Zhang, Fan ; Johnson, Leigh A. ; Hall, James ; Edwards, Melissa ; Grammas, Paula ; Oh, Esther ; Lyketsos, Constantine G. ; Rissman, Robert A. / A Precision Medicine Model for Targeted NSAID Therapy in Alzheimer's Disease. In: Journal of Alzheimer's disease : JAD. 2018 ; Vol. 66, No. 1. pp. 97-104.
@article{53b0442bec654f35977ac322dabd9487,
title = "A Precision Medicine Model for Targeted NSAID Therapy in Alzheimer's Disease",
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.",
keywords = "Alzheimer’s disease, bioinformatics, biomarkers, clinical trial, inflammation, precision medicine, proteomics",
author = "Sidney O'Bryant and Fan Zhang and Johnson, {Leigh A.} and James Hall and Melissa Edwards and Paula Grammas and Esther Oh and Lyketsos, {Constantine G.} and Rissman, {Robert A.}",
year = "2018",
month = "1",
day = "1",
doi = "10.3233/JAD-180619",
language = "English",
volume = "66",
pages = "97--104",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "1",

}

A Precision Medicine Model for Targeted NSAID Therapy in Alzheimer's Disease. / O'Bryant, Sidney; Zhang, Fan; Johnson, Leigh A.; Hall, James; Edwards, Melissa; Grammas, Paula; Oh, Esther; Lyketsos, Constantine G.; Rissman, Robert A.

In: Journal of Alzheimer's disease : JAD, Vol. 66, No. 1, 01.01.2018, p. 97-104.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A Precision Medicine Model for Targeted NSAID Therapy in Alzheimer's Disease

AU - O'Bryant, Sidney

AU - Zhang, Fan

AU - Johnson, Leigh A.

AU - Hall, James

AU - Edwards, Melissa

AU - Grammas, Paula

AU - Oh, Esther

AU - Lyketsos, Constantine G.

AU - Rissman, Robert A.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Alzheimer’s disease

KW - bioinformatics

KW - biomarkers

KW - clinical trial

KW - inflammation

KW - precision medicine

KW - proteomics

UR - http://www.scopus.com/inward/record.url?scp=85055158717&partnerID=8YFLogxK

U2 - 10.3233/JAD-180619

DO - 10.3233/JAD-180619

M3 - Article

VL - 66

SP - 97

EP - 104

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 1

ER -