Treatment of Preterm Labour

About

Overview •13 million preterm infants (before 37 weeks) are born annually1 . In developed countries preterm labour resulting in delivery represents the vast majority of those infants that die within the 1st month of life. •No discovery made in the last 20 years, has resulted in a decrease in the premature birth rate. •No treatment currently available has been shown to stop or reverse the process •Strikingly, in North America the preterm birth rate has increased from 7% in the 1980s to an all time high of 12.9% in 2008. Problem Most research has focused on identifying potential infective processes that might contribute to preterm delivery. However, clinically, Obstetricians only identify an infective process in 1/3 of patients, leaving the majority of mothers without a cause or treatment. Discovery • All pregnant mothers have a certain amount of free fetal DNA that circulates in the maternal blood. The amount increases as the mother approaches full term. • In women delivering preterm, the amount of free fetal DNA is higher at an earlier stage of the pregnancy. • We have made the novel discovery that this free fetal DNA sparks off an immune reaction in human cells through a receptor called Toll-like Receptor 9 (TLR-9). • In our animal model there is a 69% still birth/inflammation from injection of fetal DNA. This can be inhibited by the injection of specific TLR-9 inhibitors. Advantages •Advantageously, this technology demonstrates that fetal DNA is proinflammatory, and furthermore mediators of this effect have been identified. •This is the first time that a link has been made between preterm labour and specific immune regulators. • A therapeutically effective amount of an novel agent which antagonises Toll-like Receptor 9 biological activity could be administered to a patient in need of treatment, typically a pregnant mother, via any suitable route. •This finding is wholly novel and has tremendous clinical utility. Technology and Patent Status A PCT patent application has been filed; PCT/EP2009/062395 Efficacy of technology has been demonstrated in vitro, whereby fetal DNA added to the Namalwa B cell line or PMBCs has been shown to rapidly activate a variety of pro-inflammatory molecules, IL-6 and TNF. The Researchers have has further demonstrated that blocking TLR9 with Chloroquin in vivo murine model of Preterm Labour, subsequently blocked the resorption of pregnancy. In vivo results demonstrate that TLR9 knockout mice are resistant to the effects of the fetal DNA, further indicating that TLR9 is a key driver of pre-term birth. The Opportunity Trinity College Dublin are seeking to engage with a potential licensee and/or collaborator who will have the opportunity to develop and commercialise this exciting, very timely and novel technology which has the potential to decrease maternal morbidity and perinatal mortality.