Fetal Therapy Research
Center Leader: Alan Flake, MD
The convergence of technologies in modern medicine suggests that, within the next decade, essentially all anatomic and genetic diseases could be diagnosed early in gestation. Early diagnosis could enable physicians to not only treat fetal disease, but also to anticipate childhood and adult disease.
The Fetal Therapy Research Affinity Group investigates the possibilities for treating many disorders during fetal development, which may provide a therapeutic “window of opportunity” for treatment.
As part of its mission, the affinity group facilitates interaction between a diverse group of Children’s Hospital investigators interested in fetal biology and therapy. Investigators focus on fetal diagnosis and treatment, maternal aspects of fetal therapy, new methods of minimally invasive surgical or fetoscopic intervention, treatment of anatomic malformations and fetal stem cell or gene therapy.
Fetal therapy research is focused on a number of common fetal anatomic malformations, most notably prenatal surgical closure of myelomeningocele (MMC), a condition in which the backbone and spinal canal do not close before birth. Children’s Hospital is one of three surgical centers in an ongoing federally sponsored clinical trial designed to compare prenatal surgical closure of MMC with standard postnatal treatment.
As part of this research endeavor, the affinity group recently developed an experimental MMC model that closely parallels the human form of the disease. This model is expected to allow for a more in-depth study of MMC and perhaps lead to new treatment strategies.
Other areas of research focus the affinity group centers on are congenital diaphragmatic hernia, a defect in the diaphragm that allows the abdominal organs to enter the chest cavity and the potential for using fetal tracheal occlusion as a treatment for lung hypoplasia, as well as pharmacological and gene therapy approaches to pulmonary vascular hypertension. To this end, fetal therapy investigators are developing models of congenital lung malformation and abdominal wall defects.
In collaboration with the Hospital’s Center for Fetal Diagnosis and Treatment and the Fetal Cardiac Center, the Fetal Therapy Affinity Group is developing techniques for fetal cardiac intervention, specifically to open ventricular outflow tract obstructions to allow cardiac remodeling and prevent underdevelopment of the heart. Further investigations into experimental models of human anatomic defects may provide new insights into the pathophysiology of these disorders and allow for the development of new therapeutic approaches.
Hospital researchers are also investigating stem cell and gene therapy in utero. With the clinical goal of treating sickle cell disease and other hematologic disorders, investigators are aggressively pursuing strategies to increase engraftment of hematopoietic stem cells in the fetus and are making substantial progress toward improving donor cell homing to and engrafting in the fetal liver. Part of the stem cell research project involves strategies of highly selective myeloablation of the fetus using innovative reagents that specifically target hematopoietic stem cells and progenitors.
In utero gene therapy studies also involve investigations of early gestational injection methods using a high-resolution ultrasound system that allows microinjection into the amniotic space. This results in high efficiency transduction of epithelial stem cells in experimental models.