Common acid reflux drug may reduce preterm birth
Researchers have found that Lansoprazole, an over-the-counter acid
reflux drug that is often taken by pregnant women, may be a promising
therapy to reduce preterm birth.
The study, published in the journal JCI Insight also identified 12 other USFDA-approved drugs that are deemed safe in pregnancy.
While the drugs encompass a variety of modalities, the researchers said they all appear to act on biological pathways that affect the immune response, which is implicated in preterm birth.
"Inflammation clearly plays a role in initiating labour and preterm birth. Immune pathways are very significantly dysregulated in women who end up delivering preterm, and they're also dysregulated in babies who are born early," said said study senior author Marina Sirota from University of California.
"However, we have seen from our previous work that there is an interaction between the maternal and fetal immune systems and a breakdown in maternal-fetal tolerance," Sirota added.
To identify candidate drugs that might be effective in preventing preterm birth, the researchers first looked at which genes were up- or down-regulated in the blood cells of women who experienced spontaneous preterm birth to identify a gene expression "signature."
Then they looked for the opposite signature in cells that had been exposed to 1,309 different drugs, reasoning that if a drug could correct the effects that preterm birth had on the women's blood cells, the drugs might also prevent preterm birth itself.
The researchers identified 83 drug candidates, but when they excluded those found to have pregnancy risks in animal or human studies, they wound up with 13 drugs, ranked according to their "reversal score," a measure of the extent to which they were able to reverse the gene expression signature of preterm birth.
The scientists chose lansoprazole for further testing because, in addition to its high reversal score, it is available over the counter, and they know from their previous work that it affects a stress-response protein, heme oxygenase-1, that has been linked with pregnancy disorders.
Lansoprazole, which is a proton-pump inhibitor marketed as Prevacid, had the second-highest reversal score of the 13 drugs identified as being safe and effective. Progesterone was further down the list.
The researchers tested lansoprazole in pregnant mice that had been given a bacterial component to induce inflammation, which causes some fetuses to die in utero, where they are reabsorbed.
When these mice were given lansoprazole, they had more viable fetuses. Lansoprazole also worked better in these mice than progesterone.
Although it is a good measure of how inflammation affects pregnancy in mice, the researhers said the fetal resorption mouse model is not an adequate model of human preterm birth.
They said more work, including studies in people, would need to be done before lansoprazole or any of the dozen other drugs they identified could be proven effective in pregnant women at risk for preterm birth.
"This, basically, is a proof of concept that this drug has anti-inflammatory properties, which are not the properties the drug was designed for, this is a short way to get to new therapeutics for known diseases," said study author David K Stevenson.
The study, published in the journal JCI Insight also identified 12 other USFDA-approved drugs that are deemed safe in pregnancy.
While the drugs encompass a variety of modalities, the researchers said they all appear to act on biological pathways that affect the immune response, which is implicated in preterm birth.
"Inflammation clearly plays a role in initiating labour and preterm birth. Immune pathways are very significantly dysregulated in women who end up delivering preterm, and they're also dysregulated in babies who are born early," said said study senior author Marina Sirota from University of California.
"However, we have seen from our previous work that there is an interaction between the maternal and fetal immune systems and a breakdown in maternal-fetal tolerance," Sirota added.
To identify candidate drugs that might be effective in preventing preterm birth, the researchers first looked at which genes were up- or down-regulated in the blood cells of women who experienced spontaneous preterm birth to identify a gene expression "signature."
Then they looked for the opposite signature in cells that had been exposed to 1,309 different drugs, reasoning that if a drug could correct the effects that preterm birth had on the women's blood cells, the drugs might also prevent preterm birth itself.
The researchers identified 83 drug candidates, but when they excluded those found to have pregnancy risks in animal or human studies, they wound up with 13 drugs, ranked according to their "reversal score," a measure of the extent to which they were able to reverse the gene expression signature of preterm birth.
The scientists chose lansoprazole for further testing because, in addition to its high reversal score, it is available over the counter, and they know from their previous work that it affects a stress-response protein, heme oxygenase-1, that has been linked with pregnancy disorders.
Lansoprazole, which is a proton-pump inhibitor marketed as Prevacid, had the second-highest reversal score of the 13 drugs identified as being safe and effective. Progesterone was further down the list.
The researchers tested lansoprazole in pregnant mice that had been given a bacterial component to induce inflammation, which causes some fetuses to die in utero, where they are reabsorbed.
When these mice were given lansoprazole, they had more viable fetuses. Lansoprazole also worked better in these mice than progesterone.
Although it is a good measure of how inflammation affects pregnancy in mice, the researhers said the fetal resorption mouse model is not an adequate model of human preterm birth.
They said more work, including studies in people, would need to be done before lansoprazole or any of the dozen other drugs they identified could be proven effective in pregnant women at risk for preterm birth.
"This, basically, is a proof of concept that this drug has anti-inflammatory properties, which are not the properties the drug was designed for, this is a short way to get to new therapeutics for known diseases," said study author David K Stevenson.