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Treatment of Preterm Labour Inhibi&on of fetal DNA mediated pro-‐inflammatory immune responses Overview • 13 million preterm infants (before 37 weeks) are born annually1. In developed countries preterm labour resul=ng 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 =me high of 12.9% in 2008. Problem Advantages Most research has focused on iden=fying poten=al infec=ve processes that might contribute to preterm delivery. However, clinically, Obstetricians only iden=fy an infec=ve process in 1/3 of pa=ents, leaving the majority of mothers without a cause or treatment. • Advantageously, this technology demonstrates that fetal DNA is pro-‐inflammatory, and furthermore mediators of this effect have been iden=fied. • A therapeu=cally effec=ve amount of an novel agent which antagonises Toll-‐like Receptor 9 biological ac=vity could be administered to a pa=ent in need of treatment, typically a pregnant mother, via any suitable route. • This finding is wholly novel and has tremendous clinical u=lity. Discovery Maternal cell • 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. TLR-‐9 Fetal DNA • In women delivering preterm, the amount of free fetal DNA is higher at an earlier stage of the pregnancy. INFLAMMATION Infiltra&on of cells, cytokines, danger signals, onset of Preterm labour Substances that inhibit TLR-‐9 (eg. chloroquin) PRETERM DELIVERY *****already given to pregnant mothers for other diseases***** • In our animal model there is a 69% s=ll birth/inflamma=on from injec=on of fetal DNA. This can be inhibited by the injec=on of specific TLR-‐9 inhibitors. Patent granted in US with applica=ons pending in Canada and Europe US13/120,605 CA2738605 EP09783381.8 Technology and Patent Status US Patent US13/120,605 is granted, with applica=ons pending in the Canada and Europe 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 ac=vate a variety of pro-‐inflammatory molecules, IL-‐6 and TNF. The Researchers have has further demonstrated that blocking TLR9 with Chloroquine in vivo murine model of Preterm Labour, subsequently blocked the resorp=on of pregnancy. Trinity College Dublin are seeking to engage with a poten=al licensee and/or collaborator who will have the opportunity to develop and commercialise this novel technology Diagnos=cs Therapeu=cs: Synthesis, Formula=on, Processing and Drug Delivery IP Status • We have made the novel discovery that this free fetal DNA sparks off an immune reac=on in human cells through a receptor called Toll-‐like Receptor 9 (TLR-‐9). The opportunity Market In vivo results demonstrate that TLR9 knockout mice are resistant to the effects of the fetal DNA, further indica=ng that TLR9 is a key driver of pre-‐ term birth Scharfe-‐Nugent et al. J. Immunol. 2012 Jun 1;188(11):5706-‐12. TLR9 provokes inflamma=on in response to fetal DNA: mechanism for fetal loss in preterm birth and preeclampsia. Opportunity Research collabora=on, Available to license Researcher(s) Prof Luke O’Neill Dr Andrea Scharfe Nugent Dr John O’Leary Dr Sean Daly Contact Dr. Emily Vereker, Case Manager, Life Sciences [email protected] +353 1 896 4152 Reference: LO01-‐160-‐01
