Steven Rowe first encountered cystic fibrosis as a camp counselor. After decades of effort to bring effective treatments to patients, "we're on the brink of seeing this through from vision to execution and availability," he says. Steven Rowe first encountered cystic fibrosis as a camp counselor. After decades of effort to bring effective treatments to patients, "we're on the brink of seeing this through from vision to execution and availability," he says.

After a cystic fibrosis 'miracle,' researchers are exploring ways to reach millions more

November 05, 2018
By Matt Windsor
After a series of breakthroughs that researcher Steven Rowe calls "one of the most remarkable stories in modern medicine," the majority of patients with cystic fibrosis can now be treated with highly effective therapies. The next step: adapting these treatments to COPD, asthma and a host of other conditions.

Long before researchers found the cause of cystic fibrosis — a single gene on the long arm of chromosome 7 — this inherited disease was often diagnosed with a kiss. The taste of super-salty sweat on their babies’ skin alarmed parents and sent them to their doctors. Doctors, by the early 1950s, realized that abnormal sweat was a hallmark of a disease they soon defined as cystic fibrosis, a disease so severe that most patients would die in early childhood.

The trouble with mucus

Unless you have a cold, you probably don’t give mucus a second thought. But people with cystic fibrosis can often think of little else. Thick, sticky mucus coats their airways and clogs their lungs, making breathing a chore and infections a constant threat. Salty sweat is another symptom of the same root problem: one of the body’s key hydration regulators is broken. At the dawn of the 1960s, airway clearance exercises and aggressive and frequent therapy with powerful antibiotics began to push the average lifespan higher. But children with CF like Gregory Fleming James, second son of eventual Alabama governor Fob James, still didn’t generally live past 10. Gregory didn’t even make that milestone; he died in 1967, aged 8.


This animation illustrates what happens when CFTR protein channels malfunction in cystic fibrosis. Video courtesy Cystic Fibrosis Foundation.


'The clock was always ticking'

By the early 1990s, despite new, more powerful antibiotics and the use of transplants to replace failing lungs, the average lifespan for a young adult still hovered around age 20. In those years, Steven Rowe, M.D., was a teenage counselor at a camp for children with special medical needs. He got to know “the trials and lack of effective treatments” for people with cystic fibrosis first hand. “They had to have hours of physiotherapy every day, and even if they did everything right, the disease would continue its relentless progress,” Rowe recalls. In 1989, researchers had traced the cause of cystic fibrosis to mutations in the CFTR gene, and they thought a gene therapy-based cure might be just around the corner. But the day-to-day lives of patients hadn’t much changed, says Rowe. “The clock was always ticking.”

A new kind of research center

When he came to UAB for his medical residency in 1998, Rowe was determined to find treatments that could put time back on that clock. He joined internationally recognized scientists such as Eric Sorscher, Ph.D., and J.P. Clancy, M.D., at UAB’s Gregory Fleming James Cystic Fibrosis Research Center, which had been established in 1981 during Fob James’ third year as governor. The UAB CF Center, which Rowe now directs, was one of the first such centers in the country, and it has been continually funded by the NIH and the Cystic Fibrosis Foundation ever since. The center’s basic and translational research discoveries have helped transform the disease. Today, the average lifespan for a patient with cystic fibrosis is 47 and climbing fast. Rowe now can offer a growing number of his patients highly effective drug therapies that can clear their mucus blockages, improve breathing and dramatically improve their quality of life, almost overnight.

cf registry median predicted 2016Survival rates have been climbing steadily in cystic fibrosis for decades. Image courtesy Cystic Fibrosis Foundation.

'One of the most remarkable stories in modern medicine'

“This is one of the most remarkable stories in modern medicine,” says Rowe, professor in the Division of Pulmonary, Allergy and Critical Medicine in the UAB School of Medicine and Nancy R. and Eugene C. Gwaltney Family Endowed Chair in Medical Research at UAB. In CF, genetic testing is now almost universal and mutation-based drug prescribing is standard practice. That offers a template for other diseases looking to translate the promise of precision medicine into the daily lives of patients, Rowe notes. (Matt Might, Ph.D., director of UAB’s Hugh Kaul Precision Medicine Institute, says Rowe and the CF Center were a major factor that attracted him to Birmingham.) More than once, UAB researchers pursued high-risk strategies that many in the field thought were bound to fail. Those efforts have already reaped major dividends, Rowe says.

Highly effective therapies that target the basic defect should provide therapeutic benefits for 90 percent of patients with cystic fibrosis, according to a study published by Rowe and colleagues in the New England Journal of Medicine in October 2018. And UAB researchers are exploring promising new ways to reach even those with the rarest of CF mutations. Meanwhile, they’re applying CF breakthroughs to other lung diseases, from COPD to asthma and beyond. Advances that were initially designed for only a few thousand people with cystic fibrosis could eventually reach tens of millions more.

Here's how:

mix rowe lab handsPart two: How did we get here? Cystic fibrosis drugs go from 0-90 percent effective in a few short years

 


mix bedwell 200x200Part three: Attacking nonsense mutations in cystic fibrosis and a host of other diseases

 


mix naso thumb 200x200Part four: Clinical trial for one: the promise of patient-derived assays

 


mix cf smoking 200x200Part five: From cystic fibrosis to COPD: potentiators and chronic bronchitis

 


mix lasers cf 200x200Part six: Muco-vision: a new imaging approach for cystic fibrosis, asthma and beyond?