Preterm birth occurs in approximately 8% of all pregnancies, yet it accounts for nearly 75% of the morbidity and mortality seen in non- anomalous infants. Those premature babies who survive the crisis of being born prior to term are often faced with profound medical sequelae, such as low birth weight and pulmonary immaturity which are a direct result of their preterm delivery. Many of these children suffer lifelong compromise to their quality of life. The ability to manage preterm labor and prevent premature delivery may ultimately save health care dollars by reducing the need for long-term hospitalization of these infants. Prostaglandins produced by intrauterine tissues trigger uterine contractions and cervical dilatation culminating in premature expulsion of the fetus. This research proposal presents a novel strategy for the treatment of premature labor using antisense oligodeoxynucleotide technology. This approach will utilize chemically synthesized nucleic acids which are complementary to the messenger RNA encoding the enzyme cyclooxygenase-2 (COX-2) which is responsible for prostaglandin biosynthesis. These antisense oligonucleotides will bind to the COX-2 mRNA and inhibit its expression; thus, prostaglandin production cannot proceed and the signal for uterine contractions and/or cervical changes is not generated. This proposal represents a revolutionary genetic therapy-based approach to the clinical management of preterm labor. This strategy may replace or supplement current tocolytic agents which have been shown to be only marginally effective at reducing preterm birth.
| Swaisgood, C M; Zu, H X; Perkins, D J et al. (1997) Coordinate expression of inducible nitric oxide synthase and cyclooxygenase-2 genes in uterine tissues of endotoxin-treated pregnant mice. Am J Obstet Gynecol 177:1253-62 |
