International Journal of Molecular Medical Science, 2025, Vol.15, No.1, 20-32 http://medscipublisher.com/index.php/ijmms 29 9 Concluding Remarks Cystic Fibrosis (CF) is primarily caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, leading to defective ion transport across epithelial surfaces. This dysfunction disrupts chloride and bicarbonate transport, which is central to the pathogenesis of CF, resulting in chronic airway obstruction, inflammation, and infection. The metabolic pathways involving cyclic adenosine monophosphate (cAMP) are crucial for CFTR activity, and modulation of these pathways can enhance CFTR function. For instance, cAMP modulation through ATP Binding Cassette Transporter C4 (ABCC4) and phosphodiesterase-4 (PDE-4) inhibition has shown potential in increasing CFTR activity when combined with CFTR modulators like VX-770. Additionally, the nutritional status of CF patients, which is closely linked to lung function, can be influenced by CFTR modulation therapy, affecting anthropometric parameters such as body mass index (BMI) and weight. The complexity of CF pathophysiology necessitates a multifaceted therapeutic approach. While CFTR modulators have significantly improved clinical outcomes for many patients, they are not universally effective for all CFTR mutations. Combining CFTR modulators with metabolic interventions, such as cAMP modulation, offers a promising strategy to enhance CFTR function and address the variability in patient responses. Furthermore, targeting inflammation through novel anti-inflammatory strategies, including those focusing on macrophages, could complement CFTR modulation and provide a more comprehensive treatment approach. This integrated approach aims to optimize therapeutic benefits, improve quality of life, and reduce the clinical burden on CF patients. Future research should focus on developing next-generation CFTR modulators that can address a broader range of CFTR mutations and improve the efficacy of existing treatments. Personalized medicine approaches, utilizing patient-derived models, can aid in tailoring therapies to individual patient needs, ensuring optimal therapeutic outcomes. Additionally, long-term studies are needed to understand the impact of CFTR modulators on nutritional status and overall health, as well as to identify and manage any emerging side effects. Continued innovation in anti-inflammatory treatments and metabolic interventions will be crucial in enhancing the quality of life and long-term outcomes for CF patients, transforming CF from a fatal disease to a manageable chronic condition. Acknowledgments We would like to thank MedSci Publisher continuous support throughout the development of this study. Conflict of Interest Disclosure The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Bacalhau M., Camargo M., Magalhães-Ghiotto G., Drumond S., Castelletti C., and Lopes-PachecoM., 2023, Elexacaftor-tezacaftor-ivacaftor: a life-changing triple combination of CFTR modulator drugs for cystic fibrosis, Pharmaceuticals, 16(3): 410. https://doi.org/10.3390/ph16030410 Bailey J., Rozga M., McDonald C., Bowser E., Farnham K., Mangus M., Padula L., Porco K., and Alvarez J., 2020, Effect of CFTR modulators on anthropometric parameters in individuals with cystic fibrosis: an evidence analysis center systematic review, Journal of the Academy of Nutrition and Dietetics, 121(7): 1364-1378. https://doi.org/10.1016/j.jand.2020.03.014 Bakaj I., and Pocai A., 2023, Metabolism-based approaches for autosomal dominant polycystic kidney disease, Frontiers in Molecular Biosciences, 10: 1126055. https://doi.org/10.3389/fmolb.2023.1126055 Bardin P., Sonneville F., Corvol H., and Tabary O., 2018, Emerging microRNA therapeutic approaches for cystic fibrosis, Frontiers in Pharmacology, 9: 1113. https://doi.org/10.3389/fphar.2018.01113 Bodas M., and Vij N., 2019, Adapting proteostasis and autophagy for controlling the pathogenesis of cystic fibrosis lung disease, Frontiers in Pharmacology, 10: 20. https://doi.org/10.3389/fphar.2019.00020 Buzatto A.M,, Jabar M., Nizami I., Dasouki M., Li L., and Rahman A., 2020, Lipidome alterations induced by cystic fibrosis, CFTR mutation, and lung function, Journal of Proteome Research, 42(1): 15-31. https://doi.org/10.1021/acs.jproteome.0c00556
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