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Sodium channel blocker may benefit cystic fibrosis patients

Washington, May 18 (ANI): Researchers at Parion Sciences in Durham, N.C, say that a novel therapy, which prevents the build-up of mucous by increasing airway hydration, may prove beneficial to cystic fibrosis patients.

“Our results suggest that we have identified a new agent that acts directly on a specific pathway, which is involved in the development of cystic fibrosis,” said lead author Dr. Andrew Hirsh, senior director of drug discovery and preclinical development for Parion Sciences.

In individuals with cystic fibrosis, the hydration level of the airway is altered and the airway mucous builds up, interfering with normal respiration.

The researchers point out that one of the mechanisms causing airways to not clear mucous correctly in these patients involves the body’s natural homeostasis of sodium which, when absorbed too quickly from the surface of the airway, causes moisture to become absorbed too quickly.

“Cystic fibrosis patients have a genetic ion transport defect, which decreases the hydration level on the airway surface and therefore reduces the body’s ability to effectively clear mucous, which is a primary defence mechanism of the respiratory system. Diminished mucous clearance leads to chronic respiratory infection and impaired pulmonary function. Currently there are no therapies available to specifically target this channel in patients with cystic fibrosis,” Dr. Hirsh said.

The researcher has revealed that the aerosol-based therapy tested during the study uses a specific epithelial sodium channel-blocking agent called GS-9411, which prevents sodium from being absorbed across the airway, allowing the surface to remain moist.

He says that the increase in moisture allows individuals to more effectively clear the airway of mucous and infectious agents.

This study was performed during the pre-clinical stage of development to compare GS-9411 to an established epithelial sodium channel blocker, called amiloride.

During the study, the researchers applied GS-9411 to airway surface cells grown in the lab, and assessed the potency and reversibility of the drug on these cells.

Dr. Hirsh and his colleagues observed that GS-9411 allowed the cells to retain liquid for more than eight hours.

The researchers also revealed that concurrent studies on animals showed the agent to enhance mucous clearance for more than four hours.

Dr. Hirsh said that the results of their study offered new hope for cystic fibrosis sufferers.

“The potency and the length of time that the drug was effective in cells and in animal studies was an outstanding feature that distinguishes this compound from other agents,” he said.

The clinical phase of the drug development cycle will enable researchers to continue to refine the treatment for eventual distribution to cystic fibrosis patients.

“GS-9411 administered by aerosol can effectively increase airway surface liquid and enhance mucous clearance in an animal model. The results demonstrate that GS-9411 warrants further investigation as a new drug therapy to decrease respiratory infection and improve pulmonary function,” he said.

A presentation on the study’s findings was made during the American Thoracic Society’s 105th International Conference in San Diego on Sunday, May 17.  (ANI)

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