The earliest medicine: Combating congenital defects

Published in DukeMed, Summer 2006

(Sidebar to “Saving the Smallest“)

Physicians are getting better and better at treating infants who, whether premature or full-term, enter the world with medical problems. But Duke researchers like Erik Meyers, MD, and Margaret Kirby, PhD, are chasing the Holy Grail of early-life medicine: preventing the problem before the sperm meets the egg.

Both Meyers and Kirby study the causes of congenital heart defects, which result in more deaths in the first year of life than any other birth defect.

Because the heart forms in the embryo in the first two months of gestation, often before the mother knows she’s pregnant, it’s also one of the earliest defects possible.

Kirby’s lab focuses on the development of the arterial pole of the heart. Following her breakthrough discovery of neural crest cells’ role in normal heart development, a second group of myocardial cells that form the arterial pole were discovered to be involved in many classes of conotruncal (outflow tract) malformations.

Her next step will be to study the “nature or nurture” causes behind the defects in various animal models.

Meanwhile, Meyers and his team are investigating heart formation in mouse embryos who suffer from defects similar to those found in humans, hoping to pinpoint which genes contribute to a specific congenital problem.

Already, Meyers has found clues to what goes wrong with a collection of cells in pulmonary atresia to prevent the pulmonary artery from forming, as well as linkages between the Fgf8 gene and DiGeorge syndrome, another common congenital heart defect.

Meyers says the likely benefit of such work will be to “develop insight into which environmental and genetic factors could increase the risk for a family having a child with congenital heart defects” — to learn why, for example, a defect in a particular gene might make a diabetic mother more prone to having a baby with heart problems.

“Medicine has gotten pretty good at doing the heart surgeries [to repair abnormalities],” Meyers says, “but by that point, the ballgame is over. You already have the heart defect. What we’d like to do ultimately is to prevent them from occurring.”

Copyright 2006 DukeMed