Curcumin, a compound in turmeric, the spice that colors curry and mustard yellow, appears to have the potential to treat cystic fibrosis, according to a Yale University 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 cystic fibrosis, 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 M.D., a professor at the Yale University School of Medicine and senior author of the study, published April, 2004 in the journal Science.
Dr. Caplan's team discovered that curcumin corrects the defect in cystic fibrosis that leads to the manifestation of the disease. Cystic fibrosis is an inherited disease that is caused in the majority of cases by a mutation in the Delta-F508 gene that subsequently produces a misfolded Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein. This leads to failure of the CFTR, a chloride channel that transports chloride ions and water in and out of the cell, to reach its place on the cell surface. The result is a disease characterized by an overproduction of thick mucus which clogs the lungs and gastrointestinal tract, which ultimately leads to respiratory failure and premature death.
The research team, led by Yale professors Michael Caplan, MD and Marie Egan, MD, found that the Delta-F508 defect is corrected in tissue culture by administration of curcumin, which releases the CFTR protein from its inappropriate compartment within the cell and allows the CFTR to move to the cell surface. When the compound was tested in mice with the genetic defect, nasal and rectal epithelia regained near normal function and the mice survived nearly as long as normal mice.
Dr Caplan commented, “While these data are very encouraging, it is much too early to say whether curcumin will offer an effective treatment for most people with CF. In the next phase of this research, we will work to determine precisely how curcumin is achieving these effects and to optimize its potential as a possible drug. Plans are underway for a human clinical trial of curcumin, which will be carried out under the auspices of Cystic Fibrosis Foundation Therapeutics, Inc."
In this second phase, 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 Dr. 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.
Egan ME, Pearson M, Weiner SA, Rajendran V, Rubin D, Glockner-Pagel J, Canny S, Du K, Lukacs GL, Caplan MJ. 2. Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science. 2004 Apr 23;304(5670):600-2.