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

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

Sci Rep

Division of Systems Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, and Lucile Packard Children's Hospital, Palo Alto, CA, USA.

Published: March 2015

AI Article Synopsis

  • Researchers developed a new method for drug repositioning using clinical data from over 530,000 patients, incorporating 9.4 million lab tests alongside genomic information.
  • Their approach outperformed traditional genomic-based predictive models by accurately predicting drug-disease associations, including a potential new use for the asthma drug terbutaline sulfate in treating amyotrophic lateral sclerosis (ALS).
  • In zebrafish experiments, terbutaline sulfate demonstrated protective effects on nerve degeneration, suggesting its therapeutic potential could be mediated through β2-adrenergic receptors.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894399PMC
http://dx.doi.org/10.1038/srep08580DOI Listing

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