Inside Pediatrics Fall/Winter 2024

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

Isabel Virella-Lowell, M.D.

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. ●

OF CF PATIENTS WHO DO NOT QUALIFY FOR OR RESPOND TO DISEASE-MODULATING DRUGS

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Inside Pediatrics | Children’s of Alabama