Repurpose terbutaline sulfate for amyotrophic lateral sclerosis using electronic medical records

Scientific Reports
Hyojung PaikAtul J Butte

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 terbutali...Continue Reading

References

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Citations

Dec 15, 2015·Clinical Pharmacology and Therapeutics·B Chen, A J Butte
Apr 4, 2017·British Journal of Pharmacology·Y ChaD Laifenfeld
Oct 13, 2018·Nature Reviews. Drug Discovery·Sudeep PushpakomMunir Pirmohamed
Jan 15, 2020·Nature Medicine·Smadar ShiloEran Segal
Oct 7, 2017·BMC Systems Biology·Haoyang WuFuhai Li
Nov 20, 2016·CPT: Pharmacometrics & Systems Pharmacology·H PaikA J Butte
Aug 19, 2020·Alzheimer's Research & Therapy·Justin BauzonJeffrey Cummings
Oct 28, 2017·Frontiers in Pharmacology·Yuhei NishimuraHideaki Hara
Feb 6, 2020·Clinical Pharmacology and Therapeutics·Hua XuQingxia Chen
Jul 14, 2020·Medicinal Research Reviews·Jiansong FangFeixiong Cheng
Jul 22, 2019·Trends in Pharmacological Sciences·Manish D ParanjpeMarina Sirota
Apr 29, 2021·Proceedings of the National Academy of Sciences of the United States of America·Deisy Morselli GysiAlbert-László Barabási
Aug 3, 2021·Frontiers in Pharmacology·Xiaobo WangChun-Feng Liu

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Methods Mentioned

BETA
ESR

Software Mentioned

SimGEN
SimLAB
ClinDR

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