The effective treatment strategies for cystic fibrosis disease caused by the DeltaF۵۰۸ mutation: a systematic review

Background and Objective: Cystic fibrosis (CF) is a genetic disease which is caused by Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene mutations. CFTR gene is responsible for producing CFTR protein which is a channel for transporting chloride ions. DeltaF۵۰۸ is the most common mutation within this gene resulting in loss of phenylalanine amino acid, leading to impaired trafficking and misfolding of CFTR protein. As cystic fibrosis is one of the main causes of chronic diseases as well as childhood and early adulthood death, investigating effective treatment strategies is needed. Search Method: We searched PubMed, Google Scholar, Cochrane Library, and Science Direct article databases with “Cystic Fibrosis”, “DeltaF۵۰۸ mutation”, “CFTR gene”, and “Treatment” keywords from January ۲۰۰۰ to January ۲۰۲۰. ۴۲۵ articles were found, of which ۳۴۴ articles were excluded by investigating topics and ۶۹ articles by reading the abstract. We included the articles in this study if they were human conducted, original research, and treatment clinical outcomes-focused articles. In each selection stage, a different reviewer investigated the articles to confirm the unbiased selection of the articles. Finally, we came up with ۱۲ articles. Findings: Regarding the studied articles, there are different strategies for CF treatment. One of the methods is the rescue of the DeltaF۵۰۸-CFTR expression by using RXR motif-mimetics(۱), PDZ-containing protein NHE-RF۱(۲), β-Oestradiol(۳), and combination treatment with CP۷q (Hydroxypyrazoline analog) and VX-۸۰۹ (Lumacaftor drug)(۴). Another approach is based on promoting the folding and the trafficking by SAHA (Suberoylanilide hydroxamic acid)(۵), Sildenafil (Viagra)(۶), and CFcor-۳۲۵ (Quinazoline derivative)(۷). GSNO (S-Nitrosoglutathione)(۸) and Dox (Doxorubicin)(۹) are other options that improve DeltaF۵۰۸-CFTR protein maturation. In addition, Curcumin can enhance wild-type CFTR expression(۱۰, ۱۱). On the other hand, the treatment with Ivacaftor drug shows a significant decrease in pulmonary symptoms but its exact mechanism isn’t well-defined(۱۲).Conclusion:As each therapeutic strategy affects different pathways, finding a suitable combination of treatments may be a more effective therapy. Moreover, since this disease is a genetic disorder, genome-editing technologies such as CRISPR-Cas۹ can also be an efficient option.

کلیدواژه ها:

Cystic Fibrosis ، DeltaF۵۰۸ mutation ، CFTR gene ، Treatment