For four decades, University doctors have been extending life for those with cystic fibrosis
Whoever said there was a finite amount of energy in the universe has not met Dylan Mertz. This six-year-old just can’t get enough of life. He plays soccer and baseball. He loves to learn just about anything, and then tell you all about it. As far as he’s concerned, everyone in the world falls into one of two categories: friend or future friend.
But life was not always this way. When he was born, Dylan had distressingly poor muscle tone. After a couple of months he started to lose weight—even though he was getting plenty of food. When he was five months old his parents, Pam and Lou Mertz, brought him from their home in St. Michael to the University of Minnesota to be tested for cystic fibrosis. They had read about the inherited disease on Internet pages filled with stories of disrupted lives and early deaths.
Dylan tested positive
“It was sheer terror,” Pam Mertz recalls. “It was like falling off a cliff into an abyss of we didn’t know what.”
But Carlos Milla, M.D., who diagnosed Dylan, was reassuring. “He told us, ‘We know this is the worst day of your life, but you have to have hope,’” Pam recalls. “Immediately he gave us hope.”
Milla is the relatively new director of the Minnesota Cystic Fibrosis Center, which has been a national and international leader in cystic fibrosis clinical care for 40 years. During that time, the center—founded and directed until 1999 by internationally acclaimed cystic fibrosis expert Warren Warwick, M.D.—has helped thousands of children with cystic fibrosis grow up to live rich and productive lives. Center staff began working with the Mertz family right away to develop and carry out a plan that would help Dylan not only survive, but thrive.
“We feel very blessed to be in Minnesota,” Pam Mertz says. “We don’t mind the cold, we don’t mind the snow, because we’ve got a great team for Dylan at the U.”
A genetic typo
Cystic fibrosis (CF) is a hereditary disease caused by a typographical error in a gene that regulates the production of proteins that affect the movement of salt and water in the lining of internal organs. About one in 30 of us carries such a “typo” on one of our two copies of chromosome 7—but we don’t know it because the normal version on the other chromosome 7 covers for the faulty one. It’s only when two such faulty chromosomes get together—one from each parent—that symptoms appear.
And they are devastating. People with CF are prone to accumulate mucus in such organs as their lungs and sinuses that can attain a texture somewhere between Silly Putty and peanut butter. The effect on their bodies is like what you’d get if you tried lubricating your car’s engine with oatmeal instead of motor oil: Things clog up. Most notably, digestive enzymes get trapped in the pancreas rather than flowing into the stomach, making it hard for the body to extract nutrients from food. In addition, the deep recesses of the respiratory tract fill up with sticky goo, leading to inflammation, infection, and scarring.
For much of history, children with CF, plagued with nutritional deficiencies and loss of lung function, rarely lived to school age. “Let them die—it’s better for everybody,” was the prevailing attitude, says Warwick.
A pioneer emerges
In the 1950s a few renegade physicians began exploring ways to keep kids with CF alive. In 1955 parents and doctors joined together to form the Cystic Fibrosis Foundation as a nationwide resource for supporting families and individuals with CF, encouraging research, and disseminating knowledge about life-sustaining therapies.
At the University of Minnesota, Warwick was paying attention. Working under famed immunologist Robert Good, M.D., Ph.D., he had been studying immune system function in children with cystic fibrosis. He soon concluded that the key to survival was not improving the ability to recover from a lung infection, but rather keeping infections from cropping up in the first place. He joined the search for new and better approaches to overcoming the deadly effects of CF. With the assistance of antibiotics, lung-clearing therapies, and enzyme-packed pills, his patients gained a year, two years, a decade of life.
“The problem we have is not that CF is a disease—it’s a genetic predisposition to catching diseases,” Warwick says. “Probably the most important thing is the concept that lung disease in CF patients can be prevented, and that you should start treatment to prevent lung disease from the moment the diagnosis is made.”
That philosophy served as the founding principle for the Minnesota Cystic Fibrosis Center, established with support from the Cystic Fibrosis Foundation in the early 1960s. Warwick, who headed the center, brought a respiratory therapist in from Belgium to teach special chest-thumping techniques to clear the lungs. He set up educational programs, including a family weekend that has since been duplicated all over the world. The news spread that Minnesota was the place to be if you wanted to try to live with—rather than resign yourself to die from—cystic fibrosis.
“It was like a miracle,” Warwick says. “Word got around. CF patients came on their own.”
Along with teaching children and their families how to fight back, the center emphasized developing better strategies for doing so. It helped improve techniques for diagnosing CF. It established the world’s first computerized database of cystic fibrosis patients, a valuable resource for research to boost survival. In the early 1980s, supported by funding from the family of patient Annalisa Marzotto, Warwick invented a vibrating vest that Dylan Mertz and thousands of others with CF use daily to help clear their lungs. The Marzotto family also established an endowed chair in Annalisa’s name—a chair that Warwick held for many years before passing it along to his successor, Carlos Milla.
When the Minnesota Cystic Fibrosis Center was established, fewer than half its patients lived to be more than three years old. Today, median survival for Minnesota’s 500-some patients is close to 48 years—a record that few treatment centers in the world can even get close to.
“The Cystic Fibrosis Center is one of the gems in the Department of Pediatrics, Department of Medicine, and the University of Minnesota Children’s Hospital,” says John Schreiber, M.D., head of the Department of Pediatrics. “It has achieved national recognition with outstanding clinical care for children and adults with CF.”
Why the exceptional track record? The multidisciplinary staff attributes it to the single-minded focus on aggressively preventing and treating complications through a joint partnership. The patient, the family, and the medical experts—including nurses, nutritionists, social workers, psychologists, and physicians—all work together.
“They told us that they are the team but my husband and I are the coaches,” Pam Mertz explains. “If we even have a gut feeling, they trust that … they follow up on those hunches. ‘Please bug us,’ is the message we get.”
Less tangible but no less significant is the center’s focus on continuous improvement. Whenever a milestone is reached, staff members look for the next one to aim for. When medical advances create new opportunities to prolong life, they are there to apply them. When a patient dies, they not only grieve the loss but also try to figure out what to do differently next time.
“We’ve been developing the idea of CF as a disease that’s compatible with having grandchildren and retiring and living to an old age,” Warwick says. “When that’s the natural way of cystic fibrosis, then what we have started here will be accomplished.”
Today Warwick continues to be a pioneer as well as an ambassador for the University. He and his wife, Henrietta, recently gave $500,000 to support Medical School graduates who want to pursue Ph.D.s in basic science.
Setting the standard
“The center’s activity has grown tremendously in recent years and is moving at a fast pace—not only in clinical accomplishments but also in terms of research,” says Milla. “We’re being recognized as a benchmark center for other places.” In 2002 the center joined the Cystic Fibrosis Foundation’s Therapeutics Development Network, a group of 18 research centers of excellence that collaborate in developing new and better ways to minimize the impacts of CF.
Today a main research focus for the Minnesota Cystic Fibrosis Center is exploring health issues that emerge as children with CF increasingly live to adulthood. Working with the center’s massive patient database, maintained since 1975, center researcher Antoinette Moran, M.D., and colleagues are exploring strategies for preventing, detecting, and managing diabetes related to cystic fibrosis, which occurs in nearly one out of three adults with CF. Joanne Billings, M.D., M.P.H., is working to improve doctors’ understanding of how reproductive hormones alter the impact of CF in women. Other researchers are looking at lung transplantation, sinusitis, and gastroesophageal reflux disease in adults with the disease.
On the other end of the spectrum are efforts to improve diagnosis and treatment of CF early in life. This spring hospitals throughout Minnesota will include a test for cystic fibrosis in standard newborn screening procedures. Center researchers are also exploring ways to apply novel molecular techniques to identify factors involved in early manifestations of the disease. By pinpointing markers of disease activity, they hope to improve the ability to intervene early on, when there is a better opportunity to prevent permanent damage.
Ever since the gene involved in cystic fibrosis was identified in 1989, researchers around the world have been working to address CF at the molecular level. Minnesota researchers from a number of different departments are working together to develop a trans-genic model of cystic fibrosis in pigs.
“This is a true multidisciplinary and interscholastic enterprise, where the best minds within our institution are at work with one target in mind: cystic fibrosis,” says Milla. “In my view this is exactly what translational research is intended to do.” The effort will not only provide better model systems in which to test potential therapies, it will also lead to a better understanding of how the CF gene defect works. Eventually this could be used to help develop a molecular “fix.”
Dylan Mertz is doing what he can, too. He takes his pills. He does his therapy. And he prays every day for the CF researchers and for a cure for the illness that tries—but has so far failed—to slow him down.
“He believes very strongly that it will happen,” Pam Mertz says.
Story by Mary Hoff
Photos by Judy Olausen and Tim Rummelhoff