Magazine article Science News

Cystic Fibrosis Controversy: A New Theory Hints That Gene Therapy in the Womb Can Cure Disease

Magazine article Science News

Cystic Fibrosis Controversy: A New Theory Hints That Gene Therapy in the Womb Can Cure Disease

Article excerpt

"Cystic fibrosis is a preventable disease."

J. Craig Cohen makes the statement casually, almost as if unaware of the startling and controversial implications of his words. Yet Cohen certainly realizes that he has challenged the conventional wisdom about what causes this fatal disease and how to treat it.

"There's a large body of people out there who, if we're right, are pretty wrong," says Cohen, a scientist at Louisiana State University Medical Center in New Orleans.

In the March 1 Lancet, Cohen, Janet E. Larson of the Alton Ochsner Medical Foundation in New Orleans, and their colleagues reported that they had cured mice that have a mutant gene similar to the one that causes cystic fibrosis in people.

Surprisingly, the researchers did not permanently replace the defective gene in their mice. Instead, they temporarily added a working version of the gene to developing mouse fetuses.

About a week before the birth of each mouse, the researchers, using a novel form of gene therapy somewhat like amniocentesis, pierced the mother's amniotic sac and injected into the amniotic fluid genetically engineered viruses harboring the therapeutic gene. By breathing in this fluid, the fetuses exposed their lungs and gut to the gene, which then presumably directed cells there to produce its protein, says Cohen.

The viruses used do not integrate their genetic material into host cells, note the researchers. In fact, tests showed that the activity of the therapeutic gene in cells lasted only a few days. Yet even this brief presence, say Cohen and Larson, was enough to cure 13 out of 13 otherwise doomed mice.

The researchers conclude from this gene therapy study that cystic fibrosis is a disease in which the lungs and other organs develop improperly because of mutations in the cystic fibrosis gene, cftr. In essence, cystic fibrosis is a birth defect that leads to death years later.

Cohen and Larson believe that a normal cftr is needed during embryogenesis for the development of secretory cells that they have recently identified. Without these cells, the symptoms of cystic fibrosis develop, they contend.

This viewpoint differs sharply from the detailed picture of the disease that has emerged from other research within the last year (SN: 5/4/96, p. 279).

While cystic fibrosis can damage many organs, its hallmark in people is lung problems. Most scientists believe that mutant versions of cftr encode defective proteins that cannot properly transport chloride ions into lung cells, thus creating a buildup of salt outside them. This abnormally salty environment disables a natural antibiotic, leading to bacterial infections that trigger the production of mucus in the airways. Ultimately, lung damage from the infections and the accumulation of mucus make breathing impossible.

This perspective on cystic fibrosis has spurred gene therapists to focus on fixing lung cells by replacing mutant cftr genes with functional versions. In theory, that should reduce salt buildup and eliminate the deadly symptoms of the disease. Yet the first clinical trials of this gene therapy have not met with much success (SN: 10/28/95, p. …

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