Hospital, Medical School Work Together to Advance the Standard of Care for CF Patients

Innovations in Pediatrics - Fall 2017

Kimberly McBennett, MD, PhD

Mitch Drumm, PhD

The development of ivacaftor (Kalydeco) has revolutionized the treatment of certain patients with cystic fibrosis (CF).

“You see an improvement in their physical state, but also an increase in hope,” says Kimberly McBennett, MD, PhD, Interim Director of the Leroy W. Matthews Cystic Fibrosis Center at University Hospitals Rainbow Babies & Children’s Hospital and Assistant Professor of Pediatrics and Medicine, Case Western Reserve University School of Medicine “Before it was just treating symptoms. It’s not the same as something that actually treats the disease.”

Physician-scientists and researchers collaborating through UH Rainbow and Case Western Reserve University School of Medicine played key roles in advancing the science that led to the approval of ivacaftor.

“Even though the drug wasn’t discovered here and we weren’t the only ones doing the clinical trials, we’ve been involved in all the steps along the way,” says Mitch Drumm, PhD, Connie and Jim Brown Professor in Cystic Fibrosis Research at Case Western Reserve University School of Medicine.

In fact, the journal Cell recently named Dr. Drumm and seven other UH and School of Medicine researchers as the leading force behind the development of ivacaftor. The earliest contribution came from LeRoy W. Matthews, MD, for whom the cystic fibrosis center at UH Rainbow is now named.

“Back in the 1950s, Leroy Matthews recognized that we’re not going to get anywhere with CF if we don’t do research to identify what’s wrong,” Dr. Drumm says. “He implemented a very aggressive research strategy.”

Today, ivacaftor is approved for patients age 2 and older who have certain CF transmembrane conductance regulator (CFTR) gating mutations. It works by boosting the activity of the CFTR protein at the cell surface – a possibility first observed by Dr. Drumm and his team.

“What we found is that there are certain drugs that increased activity in the mutant state,” he says. “They would make the mutant protein work a little bit more like a normal protein.”

The pharmaceutical industry took this observation and ran with it, ultimately resulting in the drug ivacaftor. Fittingly, UH Rainbow was one of the leading sites for clinical trials of the drug.
“Patients here have an immense amount of respect and trust in their physicians,” Dr. Drumm says. “We’re lucky to have a much higher clinical trials participation than most places.”

Ivacaftor is now a mainstay of CF treatment. But for the CF team at UH Rainbow and the School of Medicine, the collaboration between basic science, clinical research and patient care continues to yield rewards.

“Dr. Drumm takes the observations we’re making from a clinical standpoint and asks how they can be studied in more depth and given back to benefit patients,” Dr. McBennett says. “One of the interesting things we’re doing now is taking the nasal cells from our patients. The scientists can grow these cells in the lab and test new medicines to see if they work on our patients’ cells.”

“We can try all the drugs in the arsenal. And that arsenal keeps growing,” Dr. Drumm says. “We can find out what drug and what combination works best before we do the trials with the patients.”

This is especially important given the small number of patients with particular CF mutations – and their often-fragile physical state.

“It’s very difficult to do a clinical trial with such small numbers of certain mutations,” Dr. McBennett says. If these particular patients are not available to participate in research study visits, being able to test their cells in the lab is wonderful.”

“That’s work that neither of us could do if we didn’t have the other,” says Dr. Drumm.