Michael Stalvey, M.D., associate professor in the Division of Pediatric Endocrinology & Diabetes at UAB, recently launched a new study of infants and children with cystic fibrosis (CF) with support from the Cystic Fibrosis (CF) Foundation. Dr. Stalvey is co-principal investigator of the "A Prospective Study to Evaluate Biological and Clinical Effects of Significantly Corrected CFTR Function in Infants and Young Children (BEGIN)" along with Bonnie Ramsey, M.D., Lucas Hoffman, M.D., Ph.D., and Sonya Heltshe, Ph.D. from the University of Washington and Seattle Children’s Hospital. This $11 million multi-center trial, including 30+ CF Centers across the US, will coordinate the study of children with CF for the next seven years, setting the framework for research priorities for years to come.
Individuals with CF are commonly recognized for complications associated with pulmonary disease and pancreatic insufficiency, eventually leading to their demise. As the life-expectancy of CF individuals continues to increase, co-morbid complications are more recognized and studied for the complex nature of pathogenesis and relationship to the function of the cystic fibrosis transmembrane conductance regulator (CFTR), a membrane chloride channel. These comorbidities include CF-related diabetes, CF-liver disease, growth restriction & CF-bone disease, and many more. Over the past decade, a new class of therapies targeting the function of CFTR demonstrated improvement in CFTR activity and chloride transport across the cell membrane. These novel medications, referred to as CFTR modulators, target cellular proteins originating from specific gene mutations responsible for CF. Recently, a new “triple combination” modulator named Trikafta (elexacaftor/tezacaftor/ivacaftor) was approved for treatment of nearly 90% of the CF population, based on their causative CFTR mutation. Although currently approved for children 12 years and older, based on successful clinical trials, approval is expected to extend down to children as young as age six soon – further development will seek to show the safety and efficacy of elexacaftor/tezacaftor/ivacaftor in even younger age groups. To prepare for that moment, Dr. Stalvey’s team of investigators will collect natural history data in these very young children with CF (less than six years), encompassing multiple facets of disease that are unique to children with CF at this age.
The investigators hope to further detail the early pathogenesis of comorbidities in CF that originate in the first years of life. Disease states, such as pancreatic exocrine destruction and eventual insufficiency, are highly prevalent beyond the first year of life. Other commonalities, like growth restriction, are affected by different factors at this age compared to later childhood. Moreover, as the use of CFTR modulator therapies migrate down to young children and infants, Dr. Stalvey and other investigators hope to demonstrate the impact of CFTR correction on the development of these complex multi-system disorders. An exhilarating hope of this improved understanding of pathogenesis is to potentially find a pivotal time to intervene in disease progression. The overarching goal is to possibly prevent the development of comorbidities, therefore improving life expectancy and quality of life.
Steven Rowe, M.D., director of the UAB Gregory Fleming James Cystic Fibrosis Research Center, and physician scientist integral to the development of CFTR modulators, stated “highly effective CFTR modulator therapy is transforming the care of older children and adults living with cystic fibrosis, and we continue to learn about the multi-faceted advantages of restoring CFTR function for these individual and their families. The BEGIN study will set the stage for the next frontier – correcting CFTR function in infants and young children, hopefully delaying the onset or even preventing the most feared complications of CF. We are incredibly encouraged by the efforts of Dr. Stalvey and the BEGIN research team to tackle this important initiative.”