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Experimental Gene Therapy Begun For Cystic Fibrosis

April 19, 1993

WASHINGTON (AP) _ Researchers have begun transferring normal genes into cystic fibrosis patients in an experiment they hope will lead to a cure for the most common fatal genetic disease in the United States.

The National Heart, Lung and Blood Institute announced Monday that a pioneering effort using a modified cold virus to treat cystic fibrosis with a type of gene therapy started last Saturday, the day after the experimental procedure was approved.

A version of an adenovirus, a common cold virus, modified to carry a normal human gene was dripped into the nose and airways of a 23-year-old man who has cystic fibrosis.

″The patient is fine. There were no adverse effects. No fever,″ said Dr. Ronald Crystal, a Cornell University researcher who developed the gene therapy technique while working at the National Institutes of Health. ″He had a big pizza for dinner last night.″

Crystal said identification of the patient was being withheld. A second patient is in isolation awaiting a second try of the technique in about a week, he said.

The NIH and the Food and Drug Administration on Friday approved Crystal’s application to treat 10 cystic fibrosis patients with the experimental technique. The experiment is being conducted at the NIH clinical center.

″This pioneering research marks the first use of gene therapy for a common genetic disorder,″ said Dr. Claude Lenfant, director of the National Heart, Lung and Blood Institute. ″If this approach works, we may finally see a cure for this lethal disease.″

For the experiment, a cold virus was disabled so it could not cause infection and then was modified to contain a normal of the human gene which is defective in cystic fibrosis patients. A solution of the virus was put into the nose of the CF patient and then dripped into his left lung using a bronchial tube.

Cystic fibrosis patients inherit a defect in what is called the cystic transmemberane conductance regulator gene. This flawed gene interferes with production of a protein that controls the flow of salt through cells lining the airways. As a result, heavy mucous builds up in the lungs, leading to inflammation, progressive lung deterioration and eventually death.

The therapy is designed to correct the work of the flawed gene by using the modified cold virus to insert a normal gene into cells of the airways. The cold virus will infect the lung cells, but will not reproduce itself to cause a spreading infection.

″We hope the virus will transfer the normal gene into the center of the cells to compensate for the abnormal gene that these people have,″ said Crystal.

He said the transferred gene will be in the nucleus of the target cells, but will not become incorporated permanently into the chromosomes. Crystal said this means that the therapy may have to be repeated periodically.

Crystal said that the same dose will be used on a second patient within a week. Eight other patients will receive the therapy, at increasing doses, later in the year.

CF affects about one in every 3,000 babies born in the United States. About one in every 20 white Americans are carriers of one copy of the defective gene and the disease occurs when a baby inherits two copies of the flawed gene. There currently are about 30,000 Americans with CF.

There is no cure for CF. Patients live an average of only 28 years. About 428 Americans died in 1989 as the result of CF.

Though CF is the most common lethal genetic disease in the United States, there currently are more Americans with sickle cell anemia, an genetic disease among blacks. About 384 Americans died of sickle cell disease in 1989. Many with sickle cell anemia are only slightly affected, however, and can live normal lifetimes with the disorder. CF is always fatal and usually before the age of 30.

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