Repurpose terbutaline sulfate for amyotrophic lateral sclerosis using electronic medical records

Hyojung Paik, Ah Young Chung, Hae Chul Park, Rae Woong Park, Kyoungho Suk, Jihyun Kim, Hyosil Kim, KiYoung Lee, Atul J. Butte

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Prediction of new disease indications for approved drugs by computational methods has been based largely on the genomics signatures of drugs and diseases. We propose a method for drug repositioning that uses the clinical signatures extracted from over 13 years of electronic medical records from a tertiary hospital, including >9.4 M laboratory tests from >530,000 patients, in addition to diverse genomics signatures. Cross-validation using over 17,000 known drug-disease associations shows this approach outperforms various predictive models based on genomics signatures and a well-known "guilt-by-association" method. Interestingly, the prediction suggests that terbutaline sulfate, which is widely used for asthma, is a promising candidate for amyotrophic lateral sclerosis for which there are few therapeutic options. In vivo tests using zebrafish models found that terbutaline sulfate prevents defects in axons and neuromuscular junction degeneration in a dose-dependent manner. A therapeutic potential of terbutaline sulfate was also observed when axonal and neuromuscular junction degeneration have already occurred in zebrafish model. Cotreatment with a β2-adrenergic receptor antagonist, butoxamine, suggests that the effect of terbutaline is mediated by activation of β2-adrenergic receptors.

Original languageEnglish
Article number8580
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 2015

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Terbutaline
Electronic Health Records
Amyotrophic Lateral Sclerosis
Genomics
Neuromuscular Junction
Zebrafish
Butoxamine
Drug Repositioning
Pharmaceutical Preparations
Adrenergic Antagonists
Guilt
Tertiary Care Centers
Adrenergic Receptors
Axons
Asthma
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Repurpose terbutaline sulfate for amyotrophic lateral sclerosis using electronic medical records. / Paik, Hyojung; Chung, Ah Young; Park, Hae Chul; Park, Rae Woong; Suk, Kyoungho; Kim, Jihyun; Kim, Hyosil; Lee, KiYoung; Butte, Atul J.

In: Scientific Reports, Vol. 5, 8580, 2015.

Research output: Contribution to journalArticle

Paik, Hyojung ; Chung, Ah Young ; Park, Hae Chul ; Park, Rae Woong ; Suk, Kyoungho ; Kim, Jihyun ; Kim, Hyosil ; Lee, KiYoung ; Butte, Atul J. / Repurpose terbutaline sulfate for amyotrophic lateral sclerosis using electronic medical records. In: Scientific Reports. 2015 ; Vol. 5.
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