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Sci Rep. 2015 Mar 5;5:8580. doi: 10.1038/srep08580.

Repurpose terbutaline sulfate for amyotrophic lateral sclerosis using electronic medical records.

Author information

1
1] Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Gyeonggido, Korea [2] Division of Systems Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, and Lucile Packard Children's Hospital, Palo Alto, CA, USA.
2
Graduate School of Medicine, Korea University, Ansan, Gyeonggido, Korea.
3
Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Gyeonggido, Korea.
4
Department of Pharmacology, Brain Science &Engineering Institute, Kyungpook National University, Daegu, Korea.
5
Division of Systems Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, and Lucile Packard Children's Hospital, Palo Alto, CA, USA.

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.

PMID:
25739475
PMCID:
PMC4894399
DOI:
10.1038/srep08580
[Indexed for MEDLINE]
Free PMC Article

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