Spice Could Help Treat Cystic Fibrosis

A compound in the spice that colors curry and mustard yellow appears to have the potential to treat cystic fibrosis, according to a new study done on mice.

The active ingredient in the East Indian spice turmeric, called curcumin, is already widely used as a dietary supplement, with some evidence that it inhibits the aging of cells and inflammation.

"We know curcumin has been widely used in humans and that it's effective in mice with a version of CF, but if it also turned out to help reduce inflammation in patients at the same time, that would be a great double whammy," said Dr. Michael Caplan, a professor at the Yale University School of Medicine and senior author of the study, published Friday in the journal Science.

However, both Caplan and officials of the Cystic Fibrosis Foundation are cautioning people with the disease not to start self-dosing with curcumin.

"We don't know a lot about the long-term effects of taking this substance or how it might interact with other medications that patients are already taking," Caplan said. "Plus, since all the supplements are largely unregulated, there's uncertainty about the strength and uniformity of what they might be taking."

Still, the results in mice are promising enough that the Cystic Fibrosis Foundation and SEER Pharmaceuticals will begin a study of the compound in 24 CF patients this summer. That experiment will use a human-dose equivalent to the levels given to mice by Caplan's team, mainly to check for safety and side effects. If there are no serious consequences, more tests will be done to measure the treatment's effectiveness.

Cystic fibrosis is a genetic disorder that causes severe damage to the lungs and digestive system and affects some 30,000 people in the United States.

CF disrupts the cells that produce mucus, sweat, saliva and digestive juices. These secretions are normally thin, slippery lubricants. But in CF patients, a defective gene keeps a key protein regulator of those fluids locked inside cells rather than reaching the cells' outer membranes.

The result is that secretions are thick and sticky, causing them to block ducts and passageways, particularly in the pancreas and lungs. Typically, lung failure or infection eventually kills patients, whose average survival is now about 32 years.

Caplan and Marie Egan, a Yale pediatric lung specialist and lead author of the study, have been working together for seven years on ways to restore function to mucus cells.

In CF, mucus cells' natural quality-control system traps regulator proteins, which are misformed by a genetic flaw, but still able to do their job. Normally, the proteins create channels through cell membranes that allow salt to escape and keep mucus surfaces fluid.

Caplan suspected that by inhibiting function of the cells' holding bins for another substance, calcium, it might allow the CF protein to escape. He proved this could happen using two other inhibitor chemicals, but neither was desirable as human medicines, since one seems to promote tumors, the other breaks in DNA.

But other researchers had suggested that curcumin might have the same sort of function, "and as a major constituent in food, we felt a lot better about its potential as a therapy," Caplan said.

As it turned out, the researchers aren't sure if curcumin really works the same way as the other chemicals or if it somehow binds to the CF protein to escort it safely to the edge of the cell. But experiments in mice with CF found that only 1 in 10 of the animals being fed curcumin died, compared with 60 percent of those not treated.

Although mice have the same genetic defect as with the human disease, they die from a mucus-blocked digestive tract rather than from lung damage. Not only did more of the curcumin-treated mice survive, they also gained weight.

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