Scientists Hope They Have Discovered New Form of CF Therapy

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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cystic fibrosis therapy

Scientists have discovered a new way to treat cystic fibrosis (CF) that involves delivering artificial proteins to patients’ lung cells to replace the faulty cystic fibrosis transmembrane conductance regulator (CFTR) protein.

The finding was reported in the study, “Anion carriers as potential treatments for cystic fibrosis: transport in cystic fibrosis cells, and additivity to channel-targeting drugs,” published recently in the journal Chemical Science.

CF is a genetic disorder caused by mutations in the CFTR gene, which provides instructions to make the CFTR protein. This protein works as a channel that transports in and out of cells’ molecules with a negative electrical charge (called anions), such as chloride, which have a direct impact on the regulation of water transport and the production of mucus.

In patients with CF, the transport of anions is impaired, leading to a buildup of fluid in the lungs and other organs.

“One approach to restore anion transport to CF cells [utilizes] alternative pathways for transmembrane anion transport, including artificial anion carriers (anionophores),” the researchers wrote.

The basic idea is to deliver these anionophores to patients’ lung cells, so that these artificial molecule transporters may replace the faulty CFTR protein, and restore the transport of water and salt in and out of cells, alleviating the symptoms of CF.

According to the researchers, these anionophores, unlike other types of targeted therapies that have been developed to correct specific defects in CFTR, may be used as a form of treatment for all CF patients, either alone or in combination with other CF therapies.

In their study, researchers from the University of Bristol in collaboration with investigators from the University of Southampton, both in the U.K., designed and tested 22 different anionophores.

Researchers discovered that four of these compounds (compound 11, 12, 15, and 19) were able to effectively transport anions in and out of lung cells cultured in a lab dish in a dose-dependent manner.

Moreover, they showed that all four compounds improved the transport of anions in cells that contained the F508 deletion, the most common CFTR mutation associated with CF, when used together with lumacaftor and ivacaftor, the active ingredients of two of Vertex Pharmaceuticals’ approved CF therapies, Orkambi and Kalydeco.

“We also show that the compounds need not be toxic, which is an important issue, and that their activity can supplement the effects of recently introduced drugs, which help some CF patients through a different mechanism,” Anthony Davis, from the University of Bristol and corresponding author of the study, said in a press release.

Overall, the results “provide further evidence that anionophores, by themselves or together with other treatments that restore anion transport, offer a potential therapeutic strategy for CF,” the researchers wrote.

“There’s still a long way to go, but if the research proceeds as hoped it might lead to a genuinely effective and general treatment for CF patients over this timescale,” Davis said.