Perspektywy leczenia przyczynowego mukowiscydozy

Cystic fibrosis is a single gene disorder, inherited in an autosomal recessive manner. Occurring CFTR defect leads predominantly to production of excessively viscous mucus, dysfunction of enzymatic activity of the pancreas and increased sodium chloride content in sweat. Currently used symptomatic treatment is associated with a significant reduction in the quality of life of the patient. The “high throughput screening” technique resulted in the detection of two groups of potential medications - potentiators and amplifiers. Mutations in the CFTR gene are divided into 6 classes, depending on whether the disturbance is in the translation process, protein maturation, or CFTR channel not fulfilling its function. The first class of mutations is associated with the formation of premature STOP codon, a compound which “masks” the process is ataluren. Mutations in the second class guide misfolded protein to degradation pathway. Correctors correct protein folding process and prevent its degradation. Mutation classes III to VI are associated with abnormal operation of the CFTR channel in the cell membrane. Amplifiers improve the function of the channel. Ivacaftor (VX-770) is a transmembrane transport regulator approved for treating patients with G551D, G1244E, G1349D, G178R, G551S, S1255P, S549N and S549R mutations. The second method of treatment is the gene therapy. By using viral and non-viral vectors, new copies of gene free of the mutation causing CF are introduced into the cells. The proteins encoded by these genes allow restoration of normal cell function. However, at the moment this form of treatment is in clinical trials.