Dr. Isabel Virella-Lowell and the pulmonology team at Children’s of Alabama are working on two clinical trials to help CF patients.
The evolution of cystic fibrosis (CF) treatment is considered one of the major success stories in medicine, with average life expectancy for patients skyrocketing from early teens in the 1970s to well over 50 years today. But Children’s of Alabama specialists continue dogged efforts to help the 5% of CF patients who don’t qualify for or respond to groundbreaking disease-modulating drugs—which Children’s faculty helped develop and test—that have transformed CF treatment over recent years.
Co-directed by Isabel Virella-Lowell, M.D., and George “Marty” Solomon, M.D., the University of Alabama at Birmingham (UAB) Cystic Fibrosis Therapeutics Development Center—a joint pediatric and adult endeavor—boasts more than 25 years of prominence in CF research. Nationally recognized as one of the top centers of its kind, it’s one of only 13 national resource centers for the more than 90 clinical trial centers that comprise the CF Clinical Trials Network.
Gene mutations in an epithelial membrane protein called CFTR trigger chloride transport defects that drive CF symptoms. Much-heralded disease-modulating drugs to target those defects—including Trikafta, a triple combination therapy approved in 2019 to treat patients with the most common CF mutation—have greatly improved both health and quality of life for the vast majority of these patients, Virella-Lowell said.
But the research team wants all CF patients—about 30,000 in the United States and 70,000 worldwide—to have those same advantages.
“About 5% of patients don’t have a life-changing medication,” Virella-Lowell explained. “The answer for them will be introducing a corrected gene or fixing the CFTR gene with gene editing techniques so the epithelia will produce its own normal chloride channels. If genetic therapies are successful, they could be extended to the entire CF population. Ultimately, the goal is to develop a genetic therapy that cures cystic fibrosis.”
Two of the team’s current clinical trials are focusing on these potential approaches. One is an mRNA-CFTR therapy, while the other is an adeno-associated virus (AAV)-based CFTR gene therapy. Both are phase 1 trials to determine safety and potential side effects. Other genetic therapy trials are in the pipeline as well.
With this research, the UAB CF Therapeutics Development Center is again setting itself apart in the region. It’s one of only four centers in the Southeast conducting the mRNA genetic therapy trial and one of only three performing the AAV gene therapy trial.