Developing Molecules That Could Help Lungs of People Suffering from Cystic Fibrosis

A University at Buffalo-led research team has developed molecules that could help unclog thick, sticky mucus from the lungs of people suffering from cystic fibrosis.

The chronic disease is caused by a defective protein channel that prevents chloride ions from leaving cells and creating the watery conditions necessary to clear mucus. Researchers’ synthetic molecules offer something of a detour by binding to ions and carrying them through the cell membrane.

This binding increased a liquid layer vital for mucus clearance in cystic fibrosis cells by 50%, according to a study published Oct. 9 in Nature Chemistry.

“We found that these molecules can serve as an effective ferry to transport chloride across the cell and therefore restore the level of airway surface liquid, or ASL, to essentially that of a normal cell,” says the study’s lead author, Bing Gong, PhD. “One day, they could be leveraged into a drug that treats cystic fibrosis, a very painful and unpleasant disease.”

The inability to clear mucus makes breathing difficult and risk of infection high for the nearly 40,000 Americans living with cystic fibrous. It is one of the most common fatal genetic diseases in the United States.

“It is exciting when scientific discoveries can be applied in ways that will potentially improve the health and well-being of people with complex conditions like cystic fibrosis that have limited treatment options,” says co-author Daniel Miller, a UB PhD graduate who is now assistant professor of chemistry at Hofstra University.

Just a few decades ago, most cystic fibrosis patients died in their early adulthood. However, life expectancy is now approximately 56 and many with the disease live full life spans, thanks in part to advances in treatment.

These include a drug called Trikafta, which helps the CFTR channel funnel out ions like it’s supposed to. However, the drug is expensive and, in certain countries, not even on the market.

“Developing new treatments for cystic fibrosis treatment remains a crucial effort,” Gong says. “Our research in anion and cation binding can apply to not only cystic fibrosis, but a host of other channel diseases caused by defective ion channels.”

Sources:

Ruikai Cao, Robert B. Rossdeutcher, Yulong Zhong, Yi Shen, Daniel P. Miller, Thomas A. Sobiech, Xiangxiang Wu, Laura Sánchez Buitrago, Karishma Ramcharan, Mark I. Gutay, Miriam Frankenthal Figueira, Pia Luthra, Eva Zurek, Thomas Szyperski, Brian Button, Zhifeng Shao, Bing Gong. Aromatic pentaamide macrocycles bind anions with high affinity for transport across biomembranes. Nature Chemistry, 2023; DOI: 10.1038/s41557-023-01315-w

University at Buffalo. “Synthetic molecules can ‘ferry’ mucus-clearing ions blocked by cystic fibrosis.” ScienceDaily. ScienceDaily, 10 October 2023. <www.sciencedaily.com/releases/2023/10/231010133528.htm>.

Materials provided by University at Buffalo. Original written by Tom Dinki. Note: Content may be edited for style and length.

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