Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs

Alexander Niculescu, Helen Le-Niculescu, D. F. Levey, K. Roseberry, K. C. Soe, J. Rogers, F. Khan, T. Jones, S. Judd, M. A. McCormick, A. R. Wessel, A. Williams, S. M. Kurian, Fletcher White

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

We endeavored to identify objective blood biomarkers for pain, a subjective sensation with a biological basis, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We studied psychiatric patients, a high risk group for co-morbid pain disorders and increased perception of pain. For discovery, we used a powerful within-subject longitudinal design. We were successful in identifying blood gene expression biomarkers that were predictive of pain state, and of future emergency department (ED) visits for pain, more so when personalized by gender and diagnosis. MFAP3, which had no prior evidence in the literature for involvement in pain, had the most robust empirical evidence from our discovery and validation steps, and was a strong predictor for pain in the independent cohorts, particularly in females and males with PTSD. Other biomarkers with best overall convergent functional evidence for involvement in pain were GNG7, CNTN1, LY9, CCDC144B, and GBP1. Some of the individual biomarkers identified are targets of existing drugs. Moreover, the biomarker gene expression signatures were used for bioinformatic drug repurposing analyses, yielding leads for possible new drug candidates such as SC-560 (an NSAID), and amoxapine (an antidepressant), as well as natural compounds such as pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), and apigenin (a plant flavonoid). Our work may help mitigate the diagnostic and treatment dilemmas that have contributed to the current opioid epidemic.

Original languageEnglish (US)
JournalMolecular Psychiatry
DOIs
StatePublished - Jan 1 2019

Fingerprint

Drug Repositioning
Precision Medicine
Biomarkers
Pain
Vitamin B 12
Amoxapine
Apigenin
Pyridoxine
Somatoform Disorders
Pain Perception
Vitamin B 6
Non-Steroidal Anti-Inflammatory Agents
Post-Traumatic Stress Disorders
Computational Biology
Transcriptome
Flavonoids
Pharmaceutical Preparations
Opioid Analgesics
Antidepressive Agents
Psychiatry

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Towards precision medicine for pain : diagnostic biomarkers and repurposed drugs. / Niculescu, Alexander; Le-Niculescu, Helen; Levey, D. F.; Roseberry, K.; Soe, K. C.; Rogers, J.; Khan, F.; Jones, T.; Judd, S.; McCormick, M. A.; Wessel, A. R.; Williams, A.; Kurian, S. M.; White, Fletcher.

In: Molecular Psychiatry, 01.01.2019.

Research output: Contribution to journalArticle

Niculescu, A, Le-Niculescu, H, Levey, DF, Roseberry, K, Soe, KC, Rogers, J, Khan, F, Jones, T, Judd, S, McCormick, MA, Wessel, AR, Williams, A, Kurian, SM & White, F 2019, 'Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs', Molecular Psychiatry. https://doi.org/10.1038/s41380-018-0345-5
Niculescu, Alexander ; Le-Niculescu, Helen ; Levey, D. F. ; Roseberry, K. ; Soe, K. C. ; Rogers, J. ; Khan, F. ; Jones, T. ; Judd, S. ; McCormick, M. A. ; Wessel, A. R. ; Williams, A. ; Kurian, S. M. ; White, Fletcher. / Towards precision medicine for pain : diagnostic biomarkers and repurposed drugs. In: Molecular Psychiatry. 2019.
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