Gene Therapy Could One Day Prevent Facial Birth Defects

From the WebMD Archives

Feb. 22, 2000 (Washington) -- Researchers have developed a method to potentially block the development of cleft palate and other forms of facial birth defects by injecting specific gene products, or proteins, during a key time of development. The results, presented at the annual meeting of the American Association for the Advancement of Science, could lead to gene therapy to correct these birth defects in the womb, experts say.

In rare cases a fetus can develop a severe defect of the face and head called holoprosencephaly. The most severe cases develop only one eye in the middle of the forehead and a large snout-like protrusion, known as a proboscis, where the nose should be, says lead researcher Jill Helms, DDS, PhD. Helms is an assistant professor of orthopedic surgery at the University of California, San Francisco.

Most fetuses with this disorder die, but one in 16,000 infants is born with a less severe -- but still devastating -- form of the disorder. These infants have a cleft lip and palate, which can be partially corrected by surgery. Like other facial birth defects, this one is also associated with brain abnormalities.

The researchers knew that pregnant women who received too much vitamin A, such as those taking the acne medicine Accutane (a modified version of vitamin A), were much more likely to give birth to children with this birth defect. Since little was known about the signals that control face and brain development, Helms and her colleagues began searching for an animal that developed a similar disorder.

At first, the researchers faced a problem: They needed an animal in which they could see the effects of various treatments at all stages of development.

The answer was to use chickens. Too little vitamin A also causes birth defects, and the research team noticed that depriving developing chickens of retinoic acid -- a breakdown product of vitamin A -- caused chicks to develop without the front of the brain and without a beak -- the same parts of the head and face that are affected in humans with the disorder.


Then they wanted to see if they could repair the genetic defect by adding back retinoic acid. All of the 403 chick embryos treated with retinoic acid overcame the effects and developed normally. The chicks also developed normally when dosed with a protein called "sonic hedgehog" (named for the video-game character), which they had previously shown to be involved in the development of this birth defect in mice.

"I think her work is right at the cutting edge," says John Sauk, DDS, PhD, professor and chair of oral and maxillofacial pathology at the University of Maryland in Baltimore. Fetal surgeons are already investigating possible ways to correct birth defects in the womb, and Sauk speculates that implants similar to the one Helms used could one day help correct human birth defects.

Vital Information:

  • Researchers say that doctors may someday be able to use a gene therapy to block the development of facial birth defects.
  • So far, the researchers have been able to demonstrate similar birth defects developing in chickens that are deprived of a by-product of vitamin A. The facial defects could be reversed when the by-product, called retinoic acid, was restored. A protein called "sonic hedgehog" (named for the video-game character) also blocked the defect.
  • Although researchers still have a lot to learn about how these defects arise in people, observers note this research is "right at the cutting edge."

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