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New drug target for treating preterm labor identified in Stanford study

pregnantbelly-4Here’s one of the biggest mysteries of pregnancy: How does the uterus muscle manage to stay quiet for most of gestation, yet shift to big, strong contractions when it's time for the baby to be born?

The answer is not just a matter of scientific curiosity. Preterm birth recently surpassed infectious disease as the leading cause of death in kids under age 5 worldwide, and doctors urgently need better drugs to halt uterine contractions when a pregnant woman shows up at the hospital in early labor.

Current labor-slowing drugs delay but don't entirely prevent preterm birth. They also can have bad side effects. Because they work by blocking voltage-gated calcium channels, which are a key widget in the mechanics of muscle contraction, high doses of these drugs have a detrimental effect on other muscles around the body, especially the heart.

So a Stanford team led by David Cornfield, MD, went back to the lab bench to learn more about the biology of uterine contractions. Today, they report in Science Translational Medicine on how their findings may yield a new way to stop early labor.

The researchers focused their work on a calcium channel that they suspected fine-tuned the action of the uterine muscle. They demonstrated that this channel, called the "transient receptor potential vanilloid 4 channel," has effects that are specific to the uterus during pregnancy.

For instance, their data show greater expression of the Trpv4 gene and higher levels of the TRPV4 protein in the uterus of pregnant than non-pregnant rats. The levels fall off again after the rats give birth. Trpv4 gene expression levels were also higher in uterine tissue from pregnant than non-pregnant humans. In mouse experiments, the team also found that blocking the TRPV4 channel could reduce the ability of oxytocin, a labor-triggering hormone, to cause uterine contractions. In addition, a TRPV4-blocking chemical delayed birth in a mouse model of preterm labor.

The new findings strongly suggest that the TRPV4 calcium channel fine-tunes the sensitivity of the uterus, helping it shift from the quiet state that persists through most of pregnancy to the very strong contractions needed before birth. That means the channel could be a great target for new labor-stopping drugs. Cornfield and his colleagues are eager to continue their work to see if it can be used to develop a medication that’s safe for humans and will help more pregnancies continue all the way to term.

Previously: Stanford microbiome research offers new clues to the mystery of preterm birth, Stanford/VA study finds link between PTSD and premature birth and Maternal obesity linked to earliest premature births, says Stanford study
Photo by Teza Harinaivo Ramiandrisoa

 

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