An experimental drug aimed at preventing the most common cause of premature birth has shown some encouraging success in early animal trials, scientists from the University of Adelaide in Australia have reported.
Researchers conducted a series of experiments on pregnant mice with their creation, a non-opioid form of naloxone, the modest painkiller that also reverses the effects of other opioids. This version, called (+)-naloxone, dramatically reduced the rate of mice delivering their young prematurely or stillborn when they were exposed to a substance found in bacteria that causes inflammation. Similarly, the drug prevented newborn mice from having low birth weight when their mothers were exposed to E. coli bacteria late in their pregnancy.
"We found that by treating pregnant mice with (+)-naloxone, it provided complete protection against pre-term birth triggered by bacteria,” said senior author Professor Sarah Robertson of the university’s Robinson Research Institute in a statement. “It also protected against stillbirth and infant death shortly after birth, and led to a correction in birth weight among infants that would otherwise be born at very low birth weight."
Inflammation is a key component of what kickstarts the normal delivery process. But bacterial infections, stress, or other damage to the placenta during pregnancy can also spark an inflammatory response that leads to premature births, the authors said. While naloxone is already used to reduce inflammation, the version created by Robertson’s team specifically inhibits a receptor that signals this sort of inflammation called Toll-Like receptor 4 (TLR4).
"TLR4 is a trigger of spontaneous pre-term birth," explained Robertson. "For this reason, we wanted to test a drug known for its ability to block the actions of TLR4, to see if that would also prevent pre-term birth."
Because naloxone is already safely used in pregnant women, the researchers are hopeful their findings may point the way towards a treatment readily available for people. Better still, since this version doesn’t block opioid receptors, it should also allow doctors to use other opioids to manage labor pain.
"By the time the conditions for pre-term birth have already arisen, it's often too late for current treatments to do anything about it,” Robertson said. “What we really need is to stop the train at the station, as it were, before it can head down that track. Once it's left the station it's usually too late to stop it.”
That said, it’ll take further research, money, and time before (+)-naloxone or other similar TLR4 inhibitors could be tested in human clinical trials. And figuring out how to balance the drug’s intended effects with the infection itself is another hurdle to climb, since inflammation is a natural part of how our bodies fight off germs.
Robertson and her colleagues are eager to keep pursuing this line of research, however, especially since children born prematurely face an increased risk of death and a laundry list of chronic conditions later on in life.
"Our studies give us some encouragement that it may be possible to prevent many pre-term births, by using drugs that target the body's inflammatory mechanisms, probably in combination with antibiotics as well," Robertson concluded.
The team’s findings were published Monday in Scientific Reports.
Source: Chin P, Dorian C, Hutchinson M, et al. Novel Toll-like receptor-4 antagonist (+)-naloxone protects mice from inflammation-induced preterm birth. Scientific Reports. 2016.