Computational discovery of therapeutic candidates for preventing preterm birth

Few therapeutic methods exist for preventing preterm birth (PTB). In the US, progesterone (P4) supplementation is the only FDA-approved drug for use in preventing recurrent spontaneous PTB. However, P4 has limited effectiveness (only 1/3 of cases). To identify repositioning drug candidates, the study used a rank-based pattern-matching strategy to compare the differential gene expression signature for PTB to differential gene expression drug profiles in the Connectivity Map database and assigned a reversal score to each PTB-drug pair. Eighty-three drugs, including P4, were identified. Many of these compounds have been evaluated in the context of pregnancy, with 13 belonging to pregnancy category A or B ? indicating no known risk in human pregnancy. The drug lansoprazole (a proton-pump inhibitor) with a strong reversal score and a good safety profile was selected for validation in LPS-induced inflammation mouse model. The result showed a significant increase in fetal viability by lansoprazole compared with controls