Thursday, Apr. 22, 2004
UPDATED AT 3:48 PM EDT
Associated Press
Washington — A substance in a common spice that helps turn curry and mustard yellow may also help treat deadly cystic fibrosis, a study by Yale University scientists indicates.  Eating large doses of the substance found in turmeric — a key ingredient of curry — 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 CF specialists stressed that patients should not self-medicate. 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 children and young adults in the United States. It is estimated to affect one in every 2,500 children in Canada.

CF 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 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 cannot 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 Dr. Caplan needed a safer drug candidate.

Enter curcumin. Derived from turmeric, the East Indian yellow spice used to flavour curries and colour mustard, it has long been used in Asian folk remedies as an antiseptic, a digestive aid or a cold treatment.

Still, unproved attempts to find a medical use do show that people can tolerate fairly high doses, and it seems to inhibit calcium the way Dr. Caplan wanted.

In a series of elegant experiments, Dr. 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 per cent of curcumin-treated mice died within 10 weeks, compared with 60 per cent of untreated mice — and the survivors gained weight.

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

— Additional test-tube studies, performed with the University of Toronto, showed that 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, both Dr. Caplan and the CF Foundation's Dr. Preston Campbell stress that people should realize that treatments that help mice do not always help people.

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