Gene Therapy Relieves Lung Syndrome in Rats: Study
October 01, 2002 10:52:13 AM PST, Reuters
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An experimental gene therapy alleviates a potentially fatal lung condition, cutting the short-term death rate in half, at least in rats, results of a new study show.

Though the therapy is still in its infancy and is not yet ready for clinical trials in humans, one of the study's authors, Dr. Clifford S. Deutschman of the University of Pennsylvania in Philadelphia, told Reuters Health, "This is a promising potential therapy for a really nasty, relatively common disease."

Acute respiratory distress syndrome (ARDS) causes the lungs to collect fluid and stiffen and leads to severely low levels of oxygen in the blood. It can result from a variety of lung injuries, but many cases of ARDS occur after a person develops a wide-ranging infection called sepsis.

According to Deutschman, current approaches to treating ARDS, such as ventilators and infection control, are "supportive" rather than aimed at the syndrome itself since the cause is unknown. About 30% of people who develop ARDS die from the condition, leading to roughly 80,000 ARDS deaths each year in the US and perhaps more than half a million worldwide.

Although the cause of ARDS continues to elude doctors, the condition is known to involve inflammation, the destruction of cells lining the lungs and the accumulation of certain proteins in the lungs. A protein called HSP-70, known as a heat shock protein, can limit these three processes, so Deutschman's team, including first author Dr. Yoram G. Weiss of Hadassah Medical Center in Jerusalem, Israel, set out to see whether gene therapy involving HSP-70 would relieve ARDS.

In the study, the researchers used a harmless virus to deliver the gene for HSP-70 into the lungs of rats, including some that had an ARDS-like syndrome. The gene therapy had a dramatic effect on the rats, the researchers report in the September issue of the Journal of Clinical Investigation. Several lung symptoms, including fluid accumulation, improved, and the 48-hour death rate was cut in half.

The study demonstrates that gene therapy may have a place in the treatment of acute illnesses, according to Deutschman. He noted that gene therapy initiatives have focused for the most part on correcting health problems caused by inborn errors, such as genetic mutations. Treating such genetic disorders "requires a permanent change in someone's DNA," he said, but current methods have not been able to trigger anything but temporary changes. For ARDS, however, gene therapy needs only to make a short-term change, he said. In fact, according to Deutschman, a persistent change--in this case permanently higher levels of HSP-70--could actually be harmful.

That gene therapy worked, at least to some degree, in rats with the ARDS-like condition is "encouraging," Deutschman said, "and should provoke similar approaches to other acute disorders."

The next step, Deutschman explained, is to take another look at how HSP-70 is delivered in gene therapy. In the study, the researchers gave the treatment after they had induced sepsis, the infection that can trigger ARDS. But in the clinic, "you discover patients are septic when they get sick, not when you make them septic," Deutschman said. "We need to see if giving (gene therapy) later is beneficial." If it is not, then researchers will need to develop a new gene delivery method that works later in the course of the lung condition, Deutschman added.

In an editorial that accompanies the study, Dr. Arthur S. Slutsky of the University of Toronto in Ontario, Canada, points out that "translating HSP therapy into clinical practice will have to overcome a number of hurdles." But even though the treatment may not be as effective when given later in the course of the lung condition than it was in the rat study, one possibility, according to Slutsky, is that HSP gene therapy could be given to certain high-risk patients to prevent inflammation in the lungs.

Right now, there are no human trials planned for the gene therapy, although Deutschman said that he and his colleagues, who have a patent pending on the gene therapy, "are discussing the possibility at this time."

SOURCE: Journal of Clinical Investigation 2002;110:737-739, 801-806.