Creating a Dual-Purpose Method to Prevent Sexually-Transmitted Infections and Pregnancy
W. Mark Saltzman, Ph.D.,Goizueta Foundation Professor of Chemical and Biomedical Engineering, and Chair of Biomedical Engineering
No adequate methods exist to protect women from the transmission of Human Immunodeficiency Virus (HIV) and other sexually transmitted infections. Dr. Saltzman is designing a new intravaginal ring (IVR) for the simultaneous prevention of sexually transmitted infections and unwanted pregnancy, using materials and methods known to be safe and expected to be acceptable to women. Saltzman brings an extensive biomedical engineering background in developing drug delivery systems using materials such as safe, ultra-tiny nanoparticles and non-toxic polymers. If successful, the new IVR will slowly release contraceptive agents embedded within the ring and will also slowly release nanoparticles loaded with drugs to provide sustained protection against sexually transmitted infections.
Such sustained-release formulations have proven difficult or impossible to achieve with other IVR designs. Dr. Saltzman is working to overcome this challenge through the use of two independent mechanisms for releasing the different preventive agents, and using specially-designed nanoparticles that will safely penetrate tissue and slowly release drugs locally. This new dual prevention method has the potential to significantly reduce the 7,000 new HIV transmissions that occur in women worldwide each day, while simultaneously providing a safe, effective method of contraception.
Maintaining Ovarian Function and Hormone Production After Cancer Chemotherapy
Joshua Johnson, Ph.D., Assistant Professor of Obstetrics, Gynecology & Reproductive Sciences
Co-funded by the Department of Obstetrics, Gynecology & Reproductive Sciences
Preserving the fertility of girls and women who undergo cancer treatment is critical in ensuring quality of life after treatment. The very therapies used to kill cancer cells also kill egg cells in the patients’ ovaries. Dr. Johnson’s Program-funded study was designed to determine the feasibility of using a technology identified in his laboratory to reduce the devastating loss of ovarian function that can result from chemotherapies for cancer.
Highlighted Study Findings
A state-of-the-art technique can be used to preserve fertility, in which pieces of the ovary are removed before cancer treatment and frozen, then thawed and replaced after successful treatment. However, this strategy is not available for some types of cancer, such as ovarian cancer, because returning ovary tissue into a woman treated for ovarian cancer would risk re-introduction of ovarian cancer cells. Dr. Johnson’s study took important initial steps toward improving the survival of eggs produced by culturing ovarian tissue outside of the body, avoiding the risk of returning cancerous tissue to the patient. The findings show that this technology holds promise for developing a method for maintaining ovarian function and overall health in women who undergo cancer treatment.
Understanding a Critical Step in Human Reproduction
Harvey Kliman, M.D., Ph.D., Research Scientist in Obstetrics and Gynecology
More than 10 percent of reproductive age couples suffer from infertility, and in 20-25 percent of such couples, there is no proven cause. In many of these cases, the couples pursue assisted reproductive technology (ART). However, even using ART, fewer than 10 percent of embryos implant successfully. Abnormalities in the process of implantation undermine the effectiveness of ART. Dr. Kliman recognized the value of a test to determine if the endometrium (uterine lining) was physically capable of supporting implantation.
Highlighted Study Findings
Previous research by Dr. Kliman identified an endometrial marker that could help predict whether implantation would occur during any given assisted cycle. He found that this marker is either absent, or expressed at the wrong time in patients whose assisted attempts fail. Since the majority of endometrial samples studied thus far had been from patients seeking treatment for infertility, there was little information on the prevalence of expression abnormalities of this marker in the general female population. In research funded by the Ethel F. Donaghue Women’s Health Investigator Program, Dr. Kliman was able to evaluate expression of this marker in normal, reproductive age women compared to women with unexplained infertility to establish the incidence of this marker abnormality. In this study, Dr. Kliman found that 85% of fertile women display normal patterns of this marker expression. Among women with infertility issues, only 20% revealed normal patterns. Nearly 30% of women with fertility problems had none of this marker. Due to the direct correlation between successful embryo implantation and levels of this marker, Dr. Kliman determined that a test involving this marker could help guide the physician and patient toward the most effective infertility treatment. Based on this work, Dr. Kliman developed a test that is now widely used. Significant emotional and financial expenditures have been saved for couples utilizing this test.
Using Specialized Cells of the Placenta as Predictors of Preeclampsia
Donna M. Neale, M.D., Assistant Professor of Obstetrics and Gynecology
Preeclampsia, described as high blood pressure that occurs after the 20th week of pregnancy, is the second leading cause of maternal mortality. However, no definitive causes or predictors of this disease have been identified. The purpose of this investigation was to enhance understanding of how changes in the normal function of specialized cells of the placenta, called trophoblast cells, lead to preeclampsia.
Highlighted Study Findings
In normal placental development, trophoblast cells invade the blood vessels of the uterus, and these blood vessels dilate or become wider to carry increased blood and oxygen to the fetus. In preeclampsia, these vessels remain narrow and when tissues do not get enough oxygen, toxins are released into the blood. Dr. Neale proposed that abnormal trophoblast invasion occurs in those who develop preeclampsia, due to self-destruction of the trophoblasts. She and her team developed a trophoblast viability screen to highlight differing responses when the trophoblasts were exposed to the blood of pregnant women with normal blood pressure versus blood of pregnant women who developed preeclampsia. The results of the study showed that when trophoblasts were exposed to the serum of women who were either overtly preeclamptic or were destined to develop preeclampsia, the trophoblasts underwent accelerated self-destruction. Moreover, the results of the study suggested the existence of a blood protein profile unique to each trimester of pregnancy, changing as early as the first trimester in women destined to develop preeclampsia. Combining the trophoblast viability screen and the unique protein profile represented steps toward developing a test to identify women at risk for preeclampsia. Development of such a screening test is continuing.
Pilot Project Study was funded in 2003, Dr. Neale is now at Johns Hopkins in Baltimore, MD