Study Reveals Treatment to Reverse Cleft Palates in the Womb

Until recently, there was little hope that a cleft palate — a birth defect affecting six in 2,651 children who are born in the United States — could be dealt with until after birth. Once a child is born with the defect, which is characterized by a cleft that forms in the roof of the mouth when the tissue does not join during pregnancy, he or she must endure years of reconstructive surgery and treatment.

Rena D’Souza, D.D.S., Ph.D., professor of Dentistry at the University of Utah Health, and her team recently set out to study teeth, and how a certain pair of genes affect their formation. But instead, they stumbled upon something completely different: how those genes interact with each other at an important moment of in utero development when the palate fuses.

Science Daily covered the study:

“It was really serendipitous,” she said. “For the first time, we can show the involvement of the Wnt [gene] pathway during palate fusion.”

Like people born with a cleft palate, the two sides of the palate fail to fuse in mice lacking the gene PAX9. At the molecular level, D’Souza found another abnormality. The mice missing this gene had an increase in two genes, called Dkk1 and Dkk2, that block the Wnt signaling pathway.

Dr. D’Souza took this information and administered a pharmacological treatment that inhibited the Dkk genes from blocking the formation of the palate. She introduced the drug into the test rat’s tail at a key moment of her pregnancy. As a result, her pups had fully formed palates.

The team has more work to do to ensure that there are no adverse side affects as a result of attempting the treatment on humans. But the study has a lot of promise and offers a glimmer of hope to parents of children who are at risk of developing cleft palates in utero.