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New therapies could treat tissue swelling that afflicts cancer surgery patients and others

 

 

Every night for the past 5 years, Patricia Egan has prepared for bed by pulling on a pair of chipped foam leggings that encase her limbs from her toes to the tops of her thighs. The custommade garments, which look like something a hockey goalie might wear, are supposed to prevent her legs from swelling. But they also make her feel claustrophobic and keep her awake, says Egan, 67, a retired writer from Chico, California. In the morning, she switches to less cumbersome toe gloves and knee-high compression socks that can still be uncomfortable.

Egan needs this bothersome and costly clothing because she suffers from lymphedema, a condition in which the fluid known as lymph doesn’t drain normally from a limb or other part of the body. Many cases of lymphedema result from surgery for breast cancer and other tumors that severs the lymphatic vessels, which transport lymph and immune cells, but Egan’s is a rare inherited form. “It’s like being 8 months pregnant all the time,” she says. “Your legs feel swollen and heavy, and they just won’t move.” As the lymph pools, it can also cause a host of other health problems.

Although Egan’s compression clothing curtails swelling, it can’t reestablish her lymphatic circulation—no U.S. Food and Drug Administration–approved therapy can. That’s why she recently jumped at the chance to participate in a clinical trial at Stanford University School of Medicine in Palo Alto, California. Researchers there and at several other institutions were testing whether the drug ubenimex, a leukemia treatment used in Japan, can spur the growth of new lymphatic vessels.

Results of this phase II trial may be announced later this year, and researchers have started or are planning trials of other strategies for regenerating lymphatic vessels. If the treatments work, they could benefit many of the 5 million to 6 million people in the United States—and more than 100 million around the world—with lymphedema. Improved lymph flow could also help in conditions other than lymphedema. Recent studies have implicated poor lymphatic drainage in glaucoma, rheumatoid arthritis, atherosclerosis, Alzheimer’s disease, and other illnesses.

That lymphedema might be curable “was unthinkable a few years ago,” says developmental biologist Guillermo Oliver of Northwestern University Feinberg School of Medicine in Chicago, Illinois. The new hope reflects growing knowledge about the lymphatic system. “We are starting to understand much better the molecular principles of how lymphatic vessels work,” says vascular biologist Tatiana Petrova of the University of Lausanne in Switzerland. Researchers are also uncovering some of the molecules and cells that prevent lymphatic vessels from repairing themselves after they are damaged by cancer surgery, radiation treatment, or, in the developing world, parasite infections.

Lymphedema “starts out as a plumbing problem,” says Stanford cardiologist Stanley Rockson, who first diagnosed Egan’s lymphedema and is one of the researchers who ran the recent ubenimex trial. But over time, the uncleared lymph leads to “pretty profound changes in the structure of the affected part of the body,” he says. One consequence is fibrosis—the proliferation of connective tissue—that can stiffen and thicken the skin. Fat cells proliferate, too, adding to the swelling.






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