Targeted Therapy for Restoring CFTR Activity: From Experimental to Clinical Features

Year in Review: Cystic Fibrosis Modulator Therapy-Efficacy, Access, and Evolution.

A summary of recent literature pertaining to CFTR modulators is provided to enhance the knowledge of the growing body of evidence guiding the next era of CF care, in which disease modification at the molecular level is increasingly achievable.

Combining Gene Therapy with Current Modulator Treatments for Cystic Fibrosis: A Promising Area of Research

A potential combination between gene therapy approaches and existing modulators to improve treatment eligibility, safety, and efficacy for cystic fibrosis patients is discussed.

Journal of Cystic Fibrosis

Regional features of the cystic fibrosis pediatric population structure and pathogenetic therapy coverage with CFTR-modulators in the Southern Federal District of the Russian Federation

The available data show a signficant progress in the availability of pathogen-oriented therapy in the SFD, but there remain genetic, age-related, and institutional barriers limiting full patient coverage with highly effective CFTR-modulators.

Comment on “Translating Emerging Data for Fetal Treatment of Cystic Fibrosis”

Cystic fibrosis (CF) is a multisystem genetic disease caused by pathogenic variants in the cystic fibrosis transmembrane receptor ( CFTR ) gene, leading to abnormal function in the lungs, pancreas, intestines, and other organs. CFTR modulators (CFTRm), small molecule therapies for CF, have significantly improved disease prognosis. As a result, more patients with CF can conceive, and pregnancy has become more common. While data surrounding CFTRm use during pregnancy are limited, the significant risk of untreated CF on maternal and pregnancy outcomes means that many patients opt to continue CFTRm during gestation. In addition, CF begins to manifest before birth, with potential in-utero complications like pancreatic injury and meconium ileus. This review article summarizes pregnancy safety data, animal studies, and emerging case reports with prenatal CFTRm therapy for fetuses affected by CF. Available data are generally reassuring for patients with CF who continue CFTRm during pregnancy. Continuation has been associated with preserved maternal lung function, while discontinuation has been linked in some cases to clinical decline that resolves when therapy is restarted. These medications can cross the placenta, with fetal levels equal to or higher than maternal levels, and are present at low levels in breastmilk. Some safety concerns remain, including rare hepatotoxicity, and complications seen in animal models include development of cataracts and drug accumulation in the fetal brain. However, in a CF ferret model, in utero ivacaftor prevented intestinal disease, preserved exocrine pancreatic function, and preserved the vas deferens in male offspring. This supports the possibility that treatment before birth could protect against some fetal CF manifestations. Human data on CFTRm during pregnancy remain limited but suggest possible fetal benefits. Twenty published cases describe prenatal CFTRm use in unaffected pregnant carriers whose fetuses were diagnosed with CF. Most received standard adult dosing of elexacaftor/tezacaftor/ivacaftor (Trikafta or triple therapy) after invasive prenatal diagnosis. Among 15 fetuses with meconium ileus who were treated through maternal CFTRm during pregnancy, ultrasound findings resolved before delivery in 10 cases. Findings were less likely to resolve when treatment began later or when complications such as volvulus, meconium peritonitis, or meconium pseudocyst were already present. Among published cases, the mean gestational age at diagnosis of meconium ileus was 23.8 weeks, while treatment began at a mean of 30.4 weeks, reflecting delays in diagnosis and access to therapy. Several reports also described preserved or borderline pancreatic function and lower-than-expected sweat chloride levels. Because prenatal treatment can reduce biochemical signs of pancreatic injury, newborn screening may be falsely negative, so infants with known prenatal CF diagnoses still need postnatal diagnostic evaluation. Prenatal CFTRm therapy is promising but remains investigational. Standardized guidelines for treatment have not been created, and care should include multidisciplinary counseling, genetic confirmation of fetal CF, maternal liver function monitoring, fetal ultrasound surveillance, and postnatal follow-up. Significant unanswered questions include the optimal timing of treatment, minimum effective dose, neurodevelopmental safety, and whether treatment should continue after birth to avoid withdrawal effects. Access is also a major ethical issue because therapy is expensive and insurance delays can push treatment later into gestation. Overall, the review suggests that prenatal CFTRm may prevent or improve fetal manifestations of CF, particularly meconium ileus, but prospective studies are needed before this approach can become routine care. (Summarized from Zaretsky MV, Blumenfeld YJ, Szentpetery SS, et al Translating emerging data for fetal treatment of cystic fibrosis. Prenat Diagn. 2026;46:417-423. doi:10.1002/pd.70098)

Gene therapy for rare diseases marks a new era in precision medicine: Insights from clinical trials

Clinical evidence suggests that gene-based therapies in the management of rare diseases can achieve sustained functional benefits, reduce disease-related complications, and lessen dependence on long-term replacement or supportive treatments.