Nearly 4,000 cystic fibrosis researchers and health care professionals gathered in Orlando, Fla., Oct. 11 – 13 for the 26th North American Cystic Fibrosis Conference (NACFC), sponsored by the Cystic Fibrosis Foundation.
The annual meeting brings together scientists, doctors and caregivers from around the world to discuss recent progress in CF research, care and drug development, and exchange ideas about ways to improve the health and quality of life for people with CF.
The conference’s three plenaries — featuring talks by leading researchers and physicians on topics of major interest — were the most widely attended sessions of the conference. These included presentations on the progress of potential therapies to treat the underlying cause of CF, advances in our understanding of gastrointestinal issues in CF and new approaches to overcoming barriers to adherence to the medical regimen.
Scroll down to read summaries and watch full-length videos of the plenary sessions.
Plenary Session 1: Reversing the Basic Defect: A Vision for the Future
Speakers: Steven M. Rowe, M.D., M.S.P.H, and William R. Skach, M.D.
Steven M. Rowe, M.D., assistant professor of medicine, pediatric pulmonary medicine, and physiology and biophysics at the University of Alabama at Birmingham, gave an overview of recent advances in CF research and drug development that address the underlying cause of the disease — a defective CFTR protein produced by mutations in the CF gene.
With the help of animated videos, Rowe illustrated the role of a healthy CFTR protein in regulating the flow of salt and fluids across the cell membrane to help keep the airways clear. Rowe described how different classes of CF mutations cause the protein to malfunction in distinct ways, indicating that restoring normal CFTR function could require different therapeutic approaches to treat people with specific CF mutations.
The first drug to successfully “modulate” the faulty CF protein, Kalydeco™, was approved earlier this year for people with the G551D mutation of CF ages 6 and older. About 4 percent of the CF population in the United States has the G551D mutation. The challenge ahead, said Rowe, is to bring effective CFTR modulators to all people with CF, including the nearly 90 percent of CF patients who have at least one copy of the Delta F508 mutation.
Rowe presented early findings from the G551D Observational (GOAL) Study, which is collecting data and clinical samples on people with the G551D mutation before and after they start taking Kalydeco. Results from the GOAL Study could give researchers valuable information on how Kalydeco, and potentially other CFTR modulators, affects tissues and organ systems of people with CF and help speed the development of therapies to benefit people with other CF mutations.
Rowe also discussed the positive results from a Phase 2 trial of Kalydeco combined with the potential therapy VX-809 in people with the Delta F508 mutation. Rowe noted that this trial may pave the way for future efforts to treat the basic defect in CF by combining two or more drugs.
Following Rowe’s presentation, William R. Skach, M.D., professor of biochemistry and molecular biology at Oregon Health and Science University, focused on the Delta F508 mutation and its effect on CFTR folding. In people with this mutation, the protein does not fold correctly, and, because it is not the right shape, it does not reach its proper place on the surface of the cell.
Describing CFTR folding as a “molecular jigsaw puzzle,” Skach outlined the findings of basic research over the last two decades that have changed scientists’ understanding of the CFTR protein and what causes it to misfold. For CFTR to reach the cell surface, multiple domains of the protein must fold correctly and then fit together like pieces of a puzzle in a complex process that takes place in several different environments in the cell.
Skach discussed the challenge of developing combinations of CFTR modulators that effectively address the different distinct problems caused by the Delta F508 mutation, and pointed to current drug discovery efforts that are using novel screening technologies to find new chemical compounds that could potentially benefit people with the most common CF mutation.
Plenary Session 2: Advances in GI Aspects of CF
Speaker: Drucy S. Borowitz, M.D.
Drucy S. Borowitz, M.D., clinical professor of pediatrics at the State University of New York at Buffalo School of Medicine and Biomedical Sciences, outlined advances in our understanding and treatment of gastrointestinal (GI) aspects of CF, highlighting the similarities between the problems that occur in the respiratory and GI tracts in people with CF.
In people with CF, the GI tract is often affected by a cycle of obstruction, infection and inflammation like that seen in the lungs, and similar mechanisms create the symptoms associated with CF in both parts of the body. Borowitz explained the role of bicarbonate, which is secreted by the pancreas and liver and aids in digesting fat, promoting hydration and eradicating bacteria. People with CF who are pancreatic insufficient have decreased bicarbonate secretion.
Referring to the GOAL study discussed in the first plenary, Borowitz said that people with the G551D mutation of CF who are on Kalydeco show increased bicarbonate secretion in the upper GI, which likely contributes to the significant weight gain seen in people with CF taking Kalydeco. These encouraging findings, Borowitz noted, suggest that treatments focused on modulating the CFTR protein can improve GI as well as respiratory function.
While the standardized use of pancreatic enzyme supplements has helped reduce malnutrition in infants with CF, many babies and young children with CF still have poor growth. Borowitz discussed different CF Foundation-supported studies to address this problem, including the BONUS study, a long-term observational study aimed at better understanding the factors that interfere with good growth in infants that could lay the groundwork for new approaches to help infants with CF get off to the best start.
Plenary Session 3: Adherence … Where’s the APP for That?
Speaker: Kristin A. Riekert, Ph.D.
Nonadherence to prescribed treatments contributes significantly to poor health outcomes and increased hospitalizations among people with CF. In the final plenary session, Kristin A. Riekert, Ph.D., associate professor of medicine at Johns Hopkins University, gave an overview of the scope of the problem in the CF community, the impact of nonadherence on the health of a person with CF and new intervention strategies and emerging technologies that could help improve adherence.
Drawing on video interviews that captured the insights and experiences of three individuals with CF and a CF parent, Riekert outlined the complex and interconnected factors that affect adherence. Different factors arise in different areas and phases of life — ranging from a person’s age, mental health and the quality of family relationships to access to care, work life and peer support — and require a comprehensive response.
Riekert identified two key steps care centers can take to help reduce obstacles to adherence, including more accurately identifying people who are nonadherent with their CF treatment regimens, and exploring ways to make adherence programs more practical for people with CF, their families and CF care teams.
Emerging technologies for smart phone apps and on social networking platforms could offer people with CF new tools to easily log their activities, monitor their health and benefit from personalized, real-time feedback, making adherence to the CF treatment regimen more convenient, appealing and economical.