Analysis of a precision medicine approach to treating Parkinson's disease: Analysis of the DATATOP study.

Sid E O'Bryant, Melissa Petersen, Fan Zhang, Leigh Johnson, David Mason, James Hall

Journal: Parkinsonism & related disorders 2022;94():15-21

PMID: 34864471

Free Full Text on Elsevier Science View on PubMed

Abstract

INTRODUCTION

The aim of this study was to examine the potential application of a targeted proteomic predictive biomarker comprised predominantly of inflammatory proteins in distinguishing those who responded to a previously conducted clinical trial for Parkinson's disease (PD).

METHODS

Plasma samples obtained from a biorepository were assayed from a total of n = 520 DATATOP (Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism) clinical trial participants across treatment arms. Support vector machine analyses were conducted to distinguish responder status on primary (need for Levodopa) and secondary trial endpoints (UPDRS Motor and Total Scores).

RESULTS

For the α-tocopherol and deprenyl placebo treatment arm (TOC), the targeted proteomic biomarker was able to distinguish responder status with an accuracy (area under the curve [AUC]) of 91% for the primary endpoint while it was 100% across secondary endpoints. For the deprenyl and α-tocopherol placebo treatment arm (DEP), the AUC was 93% for the primary endpoint and 99-100% for the secondary endpoints. For the combined treatment arm, AUC was 87% for the primary and 94-96% for the secondary endpoints.

DISCUSSION

The targeted proteomic predictive biomarker was highly accurate in distinguishing responder status across treatment arms thereby supporting the application of a precision medicine approach to treating PD.

Address: Institute for Translational Research, Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, Texas, 76107, USA. Electronic address: [email protected].; Institute for Translational Research, Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, Texas, 76107, USA; Department of Family Medicine, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, Texas, 76107, USA. Electronic address: [email protected].; Institute for Translational Research, Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, Texas, 76107, USA; Department of Family Medicine, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, Texas, 76107, USA. Electronic address: [email protected].; Institute for Translational Research, Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, Texas, 76107, USA. Electronic address: [email protected].; Institute for Translational Research, Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, Texas, 76107, USA; Department of Family Medicine, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, Texas, 76107, USA. Electronic address: [email protected].; Institute for Translational Research, Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, Texas, 76107, USA. Electronic address: [email protected].

DOI: 10.1016/j.parkreldis.2021.11.027

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MeSH Terms: Antiparkinson Agents, Humans, Parkinson Disease, Precision Medicine, Proteomics, Selegiline, alpha-Tocopherol