Roanoke Times
Copyright (c) 1995, Landmark Communications, Inc.
DATE: FRIDAY, October 15, 1993 TAG: 9310150181
SECTION: NATIONAL/INTERNATIONAL PAGE: A-3 EDITION: METRO
SOURCE: Associated Press
DATELINE: BOSTON LENGTH: Medium
The approach, which uses genetically engineered cold viruses to ferry healthy genes into the body, was widely praised as a major step toward the treatment of a relentlessly fatal disease as well as a landmark in the infant field of gene therapy.
In the first tentative human experiments, researchers reversed the genetic abnormality in the noses of three people with cystic fibrosis. However, they did not attempt to fix malfunctioning cells in their lungs, the real source of the diseases' tragic course toward death.
Nonetheless, the genetic defects in the nose and lungs are the same. And the latest work suggests that this approach may well restore the lungs so they work normally.
Dr. Claude Lenfant, director of the National Heart, Lung and Blood Institute, called the work "a giant step forward."
"Unless there is something I cannot anticipate, we will get to the goal line," he said.
The research was conducted by Dr. Michael J. Welsh and colleagues from Howard Hughes Medical Institute of the University of Iowa. He presented his results Thursday at the North American Cystic Fibrosis Conference in Dallas. They will be printed next week in the journal Cell, published in Cambridge, Mass.
"I'm cautiously hopeful," Welsh said. "But I think many more questions need to be answered. The really, really important issue is safety."
Although the treatment caused no ill effects in the preliminary experiment, much larger doses would be necessary to treat cystic fibrosis, and the possible hazards are still unknown.
Cystic fibrosis occurs in one in every 2,000 or 3,000 births; 30,000 Americans - mostly whites - have the disease, which runs in families. Approximately one in every 25 white Americans carries a copy of the gene. However, the disease occurs only in those who get two copies of the bad gene.
The disease results from a mutation in the gene that produces a protein called cystic fibrosis transmembrane conductance regulator. This protein controls the flow of chloride in and out of the cells that line the airways. When the protein is missing, thick mucous builds up in the lungs, causing lung damage and eventual death, often by age 30.
In their experiments, the researchers inserted a healthy copy of the gene into an adenovirus, a common cold virus. They put the genetically altered virus into the nasal passages of volunteers with cystic fibrosis.
They found that the virus infected the nasal cells and carried the gene into them. There, the gene made its protein and corrected the chloride flow defect.
To work, the healthy gene will have to be inserted into the cells that line the lungs' air passages. This probably would mean administering the treatment through an aerosol spray or a bronchial tube.
As old lung cells die and new ones are created, the treatment would have to be repeated, probably several times a year.
Two other research teams, headed by Drs. Ronald Crystal of Cornell University and James Wilson of the University of Pennsylvania, are conducting similar experiments. They are administering gene-carrying viruses directly to the lungs.
"They should be congratulated. It's great," Wilson said of the Iowa group's findings. He has so far treated two patients but not released any results.
However, he and Crystal cautioned that much more work needs to be done.
"It's a demonstration that you can correct the abnormality in the nose, but the disease is not in the nose," said Crystal, who has treated three patients.
by CNB