International Journal of Molecular Medical Science, 2025, Vol.15, No.1, 20-32 http://medscipublisher.com/index.php/ijmms 20 Research Insight Open Access Metabolic Pathways and Therapeutic Interventions in Cystic Fibrosis Tiantian Li, Jie Zhang Institute of Life Science, Jiyang College of Zhejiang A & F University, Zhuji, 311800, Zhejiang, China Corresponding author: jie.zhang@jicat.org International Journal of Molecular Medical Science, 2025, Vol.15, No.1 doi: 10.5376/ijmms.2025.15.0003 Received: 01 Dec., 2024 Accepted: 08 Jan., 2025 Published: 29 Jan., 2025 Copyright © 2025 Li and Zhang, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Li T.T., and Zhang J., 2025, Metabolic pathways and therapeutic interventions in cystic fibrosis, International Journal of Molecular Medical Science, 15(1): 20-32 (doi: 10.5376/ijmms.2025.15.0003) Abstract This study explores metabolic pathways and therapeutic interventions in Cystic Fibrosis (CF). CF is primarily caused by mutations in the CFTR gene, leading to impaired chloride and bicarbonate transport, resulting in chronic airway obstruction, inflammation, and infection. Metabolic dysregulation plays a crucial role in the pathophysiology of CF, involving abnormalities in lipid, carbohydrate, protein, and energy metabolism. The article explores current therapeutic approaches, including CFTR modulators, nutritional support, and anti-inflammatory treatments, and introduces emerging metabolic interventions such as oxidative stress reduction, metabolic modulators, and gene editing therapies, emphasizes the importance of personalized medicine, advanced models, and microbiome modulation in CF research. Future research should focus on developing next-generation CFTR modulators and personalized therapies to improve the quality of life and long-term outcomes for CF patients. Keywords Cystic fibrosis (CF); Metabolic dysregulation; CFTR modulators; Personalized medicine; Anti-inflammatory treatment 1 Introduction Cystic Fibrosis (CF) is a life-shortening genetic disorder primarily affecting the respiratory, gastrointestinal, and reproductive systems. It is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which encodes an anion channel essential for the transport of chloride and bicarbonate ions across epithelial surfaces (Veit et al., 2016; Mall et al., 2019; Southern et al., 2020). The most common mutation, F508del, leads to the production of a misfolded CFTR protein that is degraded before reaching the cell membrane, resulting in impaired ion transport and thick, sticky mucus accumulation in various organs (Fanen et al., 2014; Mall et al., 2019; Southern et al., 2020). This defective ion transport is the root cause of the chronic infections, inflammation, and progressive lung damage observed in CF patients (Lopes-Pacheco, 2020; Southern et al., 2020). Understanding the metabolic dysregulation in CF is crucial for several reasons. Metabolic abnormalities, such as dyslipidemia, are prevalent in CF patients and contribute to disease severity and progression (Buzatto et al., 2020). For instance, CF patients exhibit significant alterations in lipid metabolism, including elevated levels of odd-chain and polyunsaturated fatty acyl lipids, which are linked to lung function decline (Buzatto et al., 2020). These metabolic changes can serve as biomarkers for disease progression and therapeutic response, aiding in the development of personalized treatment strategies (Hodos et al., 2020).Targeting metabolic pathways offers a novel therapeutic approach that could complement existing CFTR modulator therapies, potentially improving clinical outcomes for CF patients (Hanrahan et al., 2019; Buzatto et al., 2020). This study aims to link the metabolic abnormalities observed in Cystic Fibrosis (CF) with therapeutic strategies aimed at correcting these dysfunctions. By exploring the complex relationships between CFTR mutations, metabolic dysregulation, and disease progression, we highlight potential therapeutic targets and interventions to enhance the efficacy of existing treatments. This study discusses the latest advancements in CFTR modulator therapies (including correctors and potentiators) and their impact on metabolic pathways, as well as emerging therapeutic approaches that address metabolic dysregulation, providing a comprehensive overview of how these strategies can be integrated into the current treatment paradigm for CF.
RkJQdWJsaXNoZXIy MjQ4ODYzNA==