2004-04-22 16:21:00
The Associated Press

WASHINGTON - A bright yellow spice common in curry might hold a key to treating deadly cystic fibrosis.

Eating large doses of a substance found in the spice turmeric significantly cut deaths among mice with the genetic disease, and scientists soon will begin studying the effects in people.

But with the release of the Yale University research in Friday’s edition of the journal Science, cystic fibrosis specialists are trying to spread the word that patients shouldn’t self-medicate with the substance, called curcumin.

It would be hard to get very high curcumin doses from food, but it is sold as a dietary supplement. Among the concerns: No one yet knows if curcumin pills could interact dangerously with the myriad other medicines cystic fibrosis patients take.

Still, the findings are very promising, said Dr. Peter Mogayzel Jr., director of the Cystic Fibrosis Center at Baltimore’s Johns Hopkins Hospital. “This is research that really has the potential, I think, to benefit patients down the road.”

Cystic fibrosis afflicts about 30,000 American children and young adults. It attacks patients’ lungs with a thick mucus, causing life-threatening infections. CF also harms digestion and vitamin absorption as the mucus clogs other organs.

Research tackles underlying cause
Treatments to fight lung infections and improve nutrition have dramatically improved care and lengthened survival into the 30s. But they treat only symptoms. The curcumin research aims at an underlying cause of those symptoms.

In most patients, CF’s damage stems from a single genetic defect. It skews a protein called CFTR that is balances the salt content of cells lining the lungs and certain other organs.

CFTR is supposed to travel to a cell’s surface to create openings, or channels, for chloride ions to exit that cell. But cells police protein quality, trapping mutated CFTR and shuttling it to a holding bin for later destruction. Thus, chloride can’t escape, and an eventual salt buildup inside cells leads to the dangerous mucus formation.

Scientists have long studied chemicals — including the drug phenylbutyrate and a caffeine relative — that might block the cellular police long enough for CFTR to escape, because even a mutated version opens some chloride channels.

Enter Yale’s Dr. Michael Caplan. That cellular holding bin also stores calcium, which many of the cell’s protein policemen need to function. He wondered if inhibiting the bin’s release of calcium would in turn let mutated CFTR escape.

Experiments with a calcium-inhibiting chemical showed the plan worked. But that chemical spurs cancer, so Caplan hunted a safer drug candidate — and learned curcumin might inhibit calcium the same way.

Spice used in folk remedies
Derived from turmeric, the yellow spice used to flavor curries and color mustard, curcumin has long been used in folk remedies. And while human studies haven’t yet proved a medical use, they do suggest people tolerate fairly high doses.

In a series of elegant experiments, Caplan and Yale CF specialist Dr. Marie Egan showed:

• Daily curcumin slashed the death rates of CF-stricken mice.

  The mice had the same genetic defect that causes the human disease, but they quickly die of a mucus-blocked digestive tract instead of lung damage. Only 10 percent of curcumin-treated mice died within 10 weeks, compared with 60 percent of untreated mice — and the survivors gained weight.

• Electrical measurements of how well nasal tissue could secrete ions also showed “a dramatic effect,” Caplan said. Curcumin-treated mice improved from very poor levels to almost normal.

• Additional test-tube studies, performed with the University of Toronto, showed CFTR got to the cell surface and functioned after addition of curcumin.

The next step: The Cystic Fibrosis Foundation is funding a first-stage study in two dozen CF patients this summer to hunt for an appropriate dose and check for side effects.

But both Caplan and the CF Foundation stress not to try curcumin treatment on your own.

Aside from possible drug interactions, treatments that help mice don’t always help people — and because dietary supplements are largely unregulated, there’s no proof supplies are pure, they caution.

Countries like India, where turmeric consumption is high, happen to have less cystic fibrosis, because that genetic defect is most common in people of European descent. Curcumin has no genetic effect.

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