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Two new approaches to genetic emphysema.

Two new approaches to genetic emphysema

Chemicals in cigarette smoke can slowly eat away the lungs' tiny air sacs and cause deadly emphysema; so can one of the body's own enzymes, neutrophil elastase. Researchers suspect that this enzyme, secreted by white blood cells called neutrophils, helps clean up wounds, but in the lungs of certain individuals it wreaks havoc.

Normally, the liver releases an elastase-degrading protein called alpha-1 antitrypsin, or AAT, into the bloodstream, protecting body tissues. But up to 40,000 people in the United States--mostly Caucasiana and Hispanics -- lack a functioning gene for AAT. By age 40, most of these people get emphysema. By age 60, only 16 percent remain alive.

Physicians can halt the lung damage by replacing the missing AAT. But that requires weekly injections with AAT derived from human blood. (A genetically engineered form is in testing.) Another approach would replace the missing AAT gene.

Two years ago, Ronald G. Crystal and his colleagues at the National Heart, Lung, and Blood Institute in Bethesda, Md., slipped the AAT gene into mouse cartilage cells using a retrovirus carrier. The cells produced human AAT both in the test tube and when injected into the abdominal cavities of mice (SN: 8/22/87, p. 119).

Crystal now proposes two new ways to replaced the AAT gene that use the same viral carrier but different target cells.

In the "mobile liver approach," he has inserted the AAT gene into mouse and human T-lymphocytes in vitro. These easily obtained white blood cells proliferate in the test tube and, with the new gene, secrete AAT. In theory, a physician could remove some T-lymphocytes from a patient, genetically modify the cells to secrete AAT, and return them to the patient.

"There are really only two hurdles before we can do it in humans,"Crystal says. "One is we have to make sure that these T-cells make enough [AAT]. The second is to ensure safety." AAT itself seems safe: Patients receiving it in large intravenous doses suffer no serious adverse effects, Crystal says.

In his second new approach, Crystal plans to infect lung epithelial cells with an aerosol of the gene-carrying virus. His work shows the virus infects the lung cells in vitro. Survival of [virus], and it's functional, then we essentially know that [the therapy] will be successful," he says.
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Author:McKenzie, Aline
Publication:Science News
Date:Oct 7, 1989
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