Unlocking Potential: Harnessing Negative Data to Accelerate CF Research and Therapeutic Development

Cystic fibrosis (CF) is a life-shortening genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Over the past decade, the U.S. Food and Drug Administration (FDA) has approved four mutation-targeted therapies that enhance the function of the CFTR protein. These therapies have significantly improved the overall quality of life for many people with cystic fibrosis. However, it is essential to note that roughly 10% of people with CF do not benefit from these approved modulator therapies—whether due to ineligible genetic mutations, side effects, or suboptimal response—and continue to face a substantial disease burden, which affects both their physical and mental health.

Gene therapy shows great promise as a potential cure for cystic fibrosis. However, past challenges in this field underline the critical importance of ensuring safety in developing gene therapies. Additionally, safety is a significant concern for individuals with CF participating in clinical trials, as highlighted by the "Final 10% Survey" conducted by Emily's Entourage in 2021 and 2022. Negative results are a crucial source of information regarding the safety and effectiveness of gene therapies. Negative results are findings that do not show statistical significance or fail to confirm the hypothesis despite thorough experimentation. The failure to publish negative results leads to research teams repeating studies that have already shown no effect or side effects, costing time and resources that could have been allocated to a different treatment. Moreover, the lack of published negative results impacts patients who do not see clinical trials demonstrating adverse events published in peer-reviewed journals. Sharing these results is vital to prevent harm to future patients participating in a duplicate trial.

For this Special Issue, we encourage researchers to submit brief communications reporting negative results from early-stage, pre-clinical, and clinical gene therapy studies focused on CF. By highlighting these findings, we can foster transparency in research and advance gene therapy for cystic fibrosis.

References:

Emily’s Entourage. The Final 10% Survey Report [Internet]. [cited 2024 Aug 3]. Available from: https://www.emilysentourage.org/wp-content/uploads/ee-final-10-percent-survey.pdf
Kramer-Golinkoff E, Camacho A, Kramer L, Taylor-Cousar JL. A survey: Understanding the health and perspectives of people with CF not benefiting from CFTR modulators. Pediatr Pulmonol. 2022;57(5).