Fatty acid could help fight cystic fibrosis

The same fatty acid that turned salmon into a health-food sensation has the potential to extend the lives of cystic fibrosis patients and ease complications of the fatal disease, a team of Massachusetts researchers report today.

The scientists, whose findings appear in The New England Journal of Medicine, discovered that cystic fibrosis patients have dramatically altered levels of fatty acids. They have too much of one acid associated with causing inflammation, and too little of another that blocks inflammation and damage to tissue.

Though emphasizing that they have not found a cure, the researchers said they are hopeful that in eight to 10 years, cystic fibrosis patients might take doses of the good fatty acid -- a member of the heralded omega-3 family -- to slow damage to the organs targeted by cystic fibrosis: the lungs, liver, and pancreas.

They have already begun a study to determine whether symptoms can be slowed or even prevented in infants born with cystic fibrosis by feeding them baby formula boosted with the fatty acid they are lacking, known in medical shorthand as DHA.

"Once the Massachusetts trial is finished, if they can see a big change in patients with the DHA supplementation, this will be a very big deal for cystic fibrosis patients," said Robert J. Beall, president of the Cystic Fibrosis Foundation. The foundation, the National Institutes of Health, and Genzyme Corp. funded the research reported today.

The disease, which affects 30,000 children and adults in the United States and typically proves fatal before the mid-30s, has proved to be an implacable foe, even though scientists identified its genetic cause 15 years ago.

Dr. Brian P. O'Sullivan, who is presiding over the fatty acid research at UMass Memorial Medical Center in Worcester, recalled the meeting in 1989 when scientists revealed the genetic secrets of cystic fibrosis, igniting hopes that gene therapy could be the answer to an illness that had defied other approaches.

"There wasn't a dry eye in the house that day," O'Sullivan said. "Most of us came home from that meeting and told families that within five years we were going to have treatments that would cure cystic fibrosis. It turns out we were wrong, wrong, wrong."

In part, that's because cystic fibrosis is a remarkably complex disease, striking different organs and affecting the way cells do their work in a variety of ways.

And gene therapy, which looked so promising early on, turned out not to be a magic bullet. Researchers hoped they could use viruses -- especially the cold virus -- to ferry healthy genes to cells carrying the defective cystic fibrosis gene, swapping good for bad.

But the human body proved too cunning, efficiently recognizing the invading viruses and allowing only about 1 percent of them to get inside cells.

That left scientists looking for other methods of thwarting cystic fibrosis. In 1999, Dr. Steven D. Freedman of Beth Israel Deaconess Medical Center reported that mice genetically altered to have the disease had in their cells an excessive amount of arachidonic acid, known as AA, and too little DHA, or docosahexaenoic acid.

They are both fatty acids and are the building blocks of the membrane, the outside shell of a cell. Those fatty acids help guide how cells function.

With his discovery in mice, Freedman and researchers at UMass and Massachusetts General Hospital wanted to know if the same phenomenon existed in humans. So they compared tissue from 38 cystic fibrosis patients with samples from healthy people and patients with other inflammatory conditions.

They found that the cystic fibrosis patients had twice as much AA as healthy people and only half as much DHA. That imbalance likely leaves cystic fibrosis patients susceptible to the severe tissue inflammation that is a hallmark of the condition and that causes lungs and other organs to fail.

Studies by Freedman showed that giving mice large doses of DHA -- the equivalent of about 35 fish-oil pills a day for a human -- corrected the imbalance and reversed signs of the disease. But scientists aren't recommending patients suddenly begin downing copious quantities of DHA because they don't know whether it would be effective in humans, or if so, what the proper dose should be.

"If you're a parent of a cystic fibrosis patient, your child has a premature death sentence and you would do anything to prolong their life," Freedman said. "So we want to be cautious about getting people's hopes up."

For those parents, the history of hopes dashed has left them circumspect.

"About 10 years ago, they were much more certain about finding a cure and then it fizzled," said Ted Cushing of Gardner, whose daughter Emily, 23, has cystic fibrosis. "So I guess we're automatically in that mind frame that it's not going to necessarily happen immediately."

Stephen Smith can be reached at stsmith@globe.com.