Spice Substance May Fight Cystic Fibrosis Thu Apr 22, 2003 2:01 PM ET

By LAURAN NEERGAARD, AP Medical Writer

 

WASHINGTON - A substance in a common spice that helps turn curry and mustard yellow might also help treat deadly cystic fibrosis, according to a study by Yale University scientists. Eating large doses of the substance found in the spice turmeric significantly cut deaths among mice with the genetic disease. The discovery prompted the Cystic Fibrosis Foundation to fund a study on its effects in patients this summer.

 

The substance, called curcumin, is sold as a dietary supplement. But patients shouldn't self-medicate, CF specialists stressed. Among the reasons: No one yet knows if large amounts of curcumin could interact dangerously with the other medicines they take.

Still, "it's 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, trapping bacteria. Most eventually die from lung damage or infection. CF also harms digestion and vitamin absorption as the mucus clogs other organs.

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, published in Friday's edition of the journal Science, shows a possible way to attack the disease's underlying cause.

In most patients, CF's damage stems from a single genetic defect. It skews a protein called CFTR that is responsible for balancing 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.

So-called protein trafficking might fix that: Block the cellular police long enough for CFTR to reach the surface and even a mutated version could open some chloride channels. Scientists for several years have experimented with two chemicals, phenylbutyrate and a relative of caffeine, that promise to do that.

Yale's Dr. Michael Caplan tried a slightly different trafficking route. That cellular holding bin also stores calcium, which many of the cell's protein policemen need to function. Would inhibiting the bin's release of calcium in turn allow mutated CFTR time to escape?

 

Experiments with a calcium-inhibiting chemical showed the plan worked. But that chemical spurs cancer, so Caplan needed a safer drug candidate.

Enter curcumin. Derived from turmeric, the East Indian yellow spice used to flavor curries and color mustard, it has long been used in Asian folk remedies as an antiseptic, a digestive aid or a cold treatment. Still, unproven attempts to find a medical use do show people can tolerate fairly high doses, and it seems to inhibit calcium the way Caplan wanted. 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 CF Foundation and SEER Pharmaceuticals will hunt for an appropriate dose and check for side effects in a first-stage study of two dozen CF patients this summer.

 

Meanwhile, don't try curcumin on your own, stress both Caplan and the CF Foundation's Dr. Preston Campbell. Treatments that help mice don't always help people.

Aside from possibly wasting money, large curcumin doses could interact with prescription drugs, and because dietary supplements are largely unregulated, there's no proof that today's supplies are pure, they caution.