2 studies raise questions about gene therapy method


Two rigorous studies of gene therapy have found that it failed to help patients with cystic fibrosis or Duchenne muscular dystrophy.

The diseases are caused by mutated genes, and in each case the hope was that if a good gene could be added to the cells that lack it, it might correct the defect in those cells.

Scientists say that the discouraging results of the two studies show that it is time to rethink the method they are using for gene therapy, which attempts to cure diseases by adding genes to cells. But, they emphasize, they remain confident that gene therapy eventually will transform medicine.

Results from both studies were published yesterday in the New England Journal of Medicine.

The cystic fibrosis study had its origins in laboratory experiments indicating that it might be possible to cure the disease. Patients with cystic fibrosis inherit a faulty gene that is used to shuttle water and salt back and forth across cell membranes. As a result, thick secretions build up in the lung and elsewhere, and patients eventually die of lung disease.

Several years ago, investigators discovered that an inactivated cold virus could add normal genes to cultured cells of patients with cystic fibrosis. In these laboratory studies, the gene therapy corrected the cells' defect.

But in the study reported yesterday, Dr. Richard C. Boucher of the University of North Carolina and his colleagues found that the method did not work in patients.

In a study of 12 patients, the researchers used inactivated cold viruses to add genes to cells that line the nose. But, they report, the nasal cells took up so few genes that the therapy had no effect.

The muscular dystrophy study, by Dr. Arthur H.M. Burghes of Ohio State University and his colleagues, asked whether healthy muscle cells could provide genes to correct the genetic defect that causes muscles to waste away in patients with the disease. The idea was to exploit a peculiar feature of muscle cells.

Unlike other cells, which line up side by side like bricks in a wall, muscle cells fuse to become giant cells. So, the notion was, if normal muscle cells were injected into the muscles of patients with muscular dystrophy, the normal cells might fuse with the diseased cells, providing the gene, called dystrophin, that the diseased cells lack.

The method worked in animals, but the investigators found it did not work in human patients.

Gene therapy researchers said they are disheartened but not discouraged.

One, Dr. Louis Kunkel of Harvard Medical School, said that for now "we have to go back to the drawing board and find out why it didn't work."

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