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
Nov 5, 1998·The New England Journal of Medicine·S L SoignetR P Warrell
Dec 26, 2001·Nucleic Acids Research·X ChenY Z Chen
Jan 5, 2002·Expert Opinion on Investigational Drugs·C M Rodrigues, C J Steer
Sep 30, 2006·Science·Justin LambTodd R Golub
Jan 8, 2008·Nature Neuroscience·Sarah KucenasBruce Appel
Jul 16, 2008·Science·Monica CampillosPeer Bork
Jul 3, 2009·Clinical Pharmacology and Therapeutics·A P Chiang, A J Butte
Apr 8, 2011·Pharmacoepidemiology and Drug Safety·Man Young ParkRae Woong Park
Jun 10, 2011·Molecular Systems Biology·Assaf GottliebRoded Sharan
Jun 22, 2011·Briefings in Bioinformatics·Joel T DudleyAtul J Butte
Aug 19, 2011·Science Translational Medicine·Marina SirotaAtul J Butte
May 19, 2012·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Alessandra CifraAndrea Nistri
Jul 26, 2012·Clinical Pharmacology and Therapeutics·M Y ParkR W Park
Apr 16, 2014·Journal of Translational Medicine·Hyojung PaikSeong Beom Cho
May 3, 2014·Science Translational Medicine·Li LiAtul J Butte
Citations
Dec 15, 2015·Clinical Pharmacology and Therapeutics·B Chen, A J Butte
Oct 16, 2015·Neurobiology of Disease·Raymond T BartusNicholas M Boulis
Jun 9, 2016·Briefings in Bioinformatics·Santiago Vilar, George Hripcsak
Aug 16, 2016·Journal of Pharmaceutical Sciences·Jane P F Bai
Apr 4, 2017·British Journal of Pharmacology·Y ChaD Laifenfeld
Jan 25, 2017·Scientific Reports·Carmelo MiliotoMaria Pennuto
Mar 21, 2018·PloS One·Zsolt ZadorNophar Geifman
Oct 13, 2018·Nature Reviews. Drug Discovery·Sudeep PushpakomMunir Pirmohamed
Jul 23, 2019·PloS One·Alexander P LandryZsolt Zador
Jan 15, 2020·Nature Medicine·Smadar ShiloEran Segal
Jun 10, 2017·Genome Research·Myungjin JoKyoungho Suk
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
Feb 10, 2021·BMC Bioinformatics·Hailin ChenJingpu Zhang
Feb 25, 2021·JAMIA Open·Michal Ozery-FlatoChen Yanover
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