Summary - Vanderbilt Health researchers have identified several existing FDA-approved drugs that may have potential for future treatment of preterm labor, a condition in which the uterus begins contracting too early during pregnancy. Led by Shajila Siricilla, PhD, and Jennifer Herington, PhD, the research team screened 1,191 FDA-approved medications, evaluating their ability to reduce uterine muscle activity while limiting effects on vascular smooth muscle and meeting other safety and effectiveness criteria. Researchers emphasized that the findings do not mean the identified drugs are currently ready to treat preterm labor, but the study provides promising candidates for additional testing and a new approach to finding safer treatments among medications already in use. One drug of particular interest is ciclesonide, a prescription steroid used to control asthma and allergy symptoms, which demonstrated an ability to inhibit human uterine contractions and is separately being studied for its potential to help protect premature infants from a serious lung condition. Researchers say the long-term goal is not simply to temporarily stop contractions but to safely extend pregnancy when medically appropriate, giving an unborn child additional time for critical development.

HEALTH NEWS - A team of Vanderbilt Health investigators has identified several drugs with previously unrecognized potential as treatments for preterm labor, according to a paper recently published in the journal Science Translational Medicine.

 

Shajila Siricilla, PhD, Assistant Professor of Pediatrics, and Jennifer Herington, PhD, Associate Professor of Pediatrics, led a team that systematically screened 1,191 FDA-approved drugs and found that several candidates met criteria supporting further evaluation as potential treatments for preterm labor.

 

“Rather than starting with entirely new drugs, we asked whether medicines that are already FDA-approved for other conditions might have previously unrecognized effects on the uterus,” said Siricilla, the study’s lead author.

 

The investigators said preterm labor occurs when the uterus begins contracting too early in pregnancy, noting that currently, there are no FDA-approved medications in the United States specifically for stopping these contractions. FDA-approved drugs that are used off label — or prescribed for a use other than what it has been approved for — can delay delivery, but their use is often limited by side effects to the mother or fetus.

 

“Our findings do not mean that these drugs are ready to be used clinically for preterm labor; rather, they identify promising candidates for further development and demonstrate a systematic strategy for finding potentially safer and more effective treatments among medicines that already exist,” said Herington, the study’s corresponding author.

 

Drugs were screened based on their ability to inhibit uterine muscle activity, preferentially affect uterine rather than vascular smooth muscle and meet additional safety and efficacy criteria. Drug repurposing is particularly attractive because these medicines already have substantial information available about their pharmacology and clinical use, the investigators said, and this methodology encourages further research into pregnancy-specific pharmacology to identify those that check every box for safe clinical testing.

 

The research team concluded that while their findings do not change clinical care today, they represent possible improvements to drug discovery for treating preterm labor. The long-term goal, they said, is not simply to stop contractions for a short period of time, but to safely prolong pregnancy when doing so is medically appropriate.

 

Ciclesonide, a prescription steroid medication used to prevent and control asthma and allergy symptoms, may be particularly interesting because its potential relevance extends beyond delaying preterm birth. The drug is also being investigated as a potentially brain-sparing corticosteroid to prevent bronchopulmonary dysplasia, a common serious lung disease of premature infants.

 

"Our study independently identified ciclesonide for its uterine-selective activity and ability to inhibit human myometrial contractions, raising the intriguing possibility that the same repurposed drug could ultimately have relevance both before and after preterm birth,” said Herington.

 

The investigators emphasized that the additional time spent in utero can be important for fetal development, and research into achieving a medically safe gestation period is critical.

 

“Our preclinical findings provide candidates and a framework that we can now investigate more rigorously toward that goal,” said Siricilla.

 

This work was supported by Vanderbilt Office of Clinical and Translational Scientist Development and CTSA awards UL1TR000445 and KL2TR000446 from the National Center for Advancing Translational Sciences, and by the NIH grants HD088830, HD098213, HD108420, HD094946, HL164327 and HL128386.