New Genetic Link Could Help Predict Response to Cystic Fibrosis Treatment

Özge Özkaya, PhD avatar

by Özge Özkaya, PhD |

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pancreatitis in CF patients

A new study recently reported that the modifier gene called SLC26A9 may have an influence on whether cystic fibrosis (CF) patients will respond to treatment with new drugs.

The SLC26A9 gene is thought to encode for a protein found on the surface of certain types of cells and to interact with the cystic fibrosis transmembrane conductance regulator (CFTR– the gene mutated in CF patients) helping its function. There are two variants of the SLC26A9 gene in the human population, a T and a C variant.

There are also two main types of CF-causing mutations in the CFTR gene. One is called gating mutations and is seen in a smaller proportion of CF patients; these mutations cause a dysfunction in the CFTR channel encoded by the gene. A novel drug called Kalydeco (ivacaftor) is often used in these cases as it improves the function of the channel.

The second more severe type of CFTR mutation affects the majority of CF patients. These mutations not only cause a dysfunction in the CFTR channel, but also impair the channel’s ability to reach the correct localization on the cell surface. For these patients, Orkambi (lumacaftor combined with ivacaftor) is used, which is able to help with the proper localization of the CFTR channel.

The team of researchers from Canada and France found that CF patients who have the C variant of the SLC26A9 gene are more likely to have milder symptoms and respond better to new treatments compared to those who have the T variant. The team also found that patients with the C variant of the SLC26A9 gene and gating mutations in the CFTR responded better to treatment with Kalydeco.

Because these are relatively new drugs, researchers could not find enough patients to assess the association between the two SLC26A9 variants and the effect of treatment with Orkambi.

To assess this association, the team used cells from the airways of patients carrying either one or the other SLC26A9 variant and grew them in the laboratory. When cells were treated with Orkambi, researchers found that cells with the C variant responded better to treatment than those with the T variant.

The “findings support that SLC26A9 can influence the lung function in CF, especially in the context of CFTR- directed therapies,” the research team wrote in their report. “Our findings indicate that SLC26A9 airway modification requires CFTR at the cell surface, and that a common variant in SLC26A9 may predict response to CFTR-directed therapeutics.”

According to the authors, these findings constitute the first step toward personalized medicine for CF patients.

The study “Cystic Fibrosis Gene Modifier SLC26A9 Modulates Airway Response to CFTR-directed Therapeutics” was published in the scientific journal Human Molecular Genetics.