EMBL scientists have discovered the potential use of a US Food and Drug Administration-approved over-the-counter cough syrup ingredient to treat pulmonary fibrosis disease. Dextromethorphan, a common ingredient in many over-the-counter cough syrups, may show promise in treating pulmonary fibrosis -- a condition associated with a variety of serious health problems.

Researchers at EMBL Heidelberg, in collaboration with other scientists, have discovered dextromethorphan as a potential treatment for pulmonary fibrosis. Their findings, published in Science Translational Medicine, reveal that dextromethorphan can reduce lung fibrosis by interfering with the production of collagen, which causes intracellular scarring.

Pulmonary fibrosis is caused by excessive scarring due to the buildup of fibrous collagen in the lungs and typically occurs in older adults for a variety of reasons: exposure to environmental irritants such as asbestos, coal dust, and mold; side effects of chemotherapy drugs; long-term consequences of serious lung diseases such as tuberculosis; and as part of certain autoimmune or inflammatory diseases such as lupus or rheumatoid arthritis.

A new study examines the potential of dextromethorphan, a U.S. Food and Drug Administration-approved drug, to treat pulmonary fibrosis. Pulmonary fibrosis occurs when scar tissue accumulates in the lungs (scar tissue in mouse lungs, left), which is reduced after treatment with dextromethorphan (right). Image credit: Muzamil Khan and creative team/EMBL

Fibrotic scarring can cause lung tissue to stiffen, making it difficult to breathe, lowering oxygen levels in the blood and eventually leading to organ failure. The World Health Organization (WHO) estimates that 761,000 people in its European region have suffered from pulmonary fibrosis since 2019. In addition, WHO estimates that 25,000 patients have died and 496,000 healthy years have been lost due to pulmonary fibrosis.

"After learning that there was no cure for pulmonary fibrosis, I wanted to discover new drugs to treat this disease," said Muzamil Majid Khan, first author of the paper and associate researcher at EMBL.

Knowing the difficulty of developing new drugs, Muzamil M Khan and his team decided to explore those that were already approved and readily available. EMBL scientists screened a library of US Food and Drug Administration-approved drugs, which included dextromethorphan. The researchers, working with the Translational Lung Research Center (TLRC) in Heidelberg and the German Lung Research Center (DZL), used human lung cells and applied a variety of cutting-edge technologies that did not exist when many drugs were first approved.

"To screen potential anti-fibrotic drugs, we first used an optimized 'scar-in-a-jar' assay under high-throughput microscopy to identify potential drugs that inhibit collagen trafficking, and subsequently used a variety of techniques including proteomics, transcriptomics, microscopy and more to identify the drug's mechanism of action," said Khan. "The 'scar-in-a-jar' assay takes its name from the fact that it is an in vitro system for studying lung fibrosis, allowing scientists to address the complete process of collagen formation, thereby using it as a model to test the efficacy of anti-fibrotic drugs."

Preclinical trial results are promising

Through these previous experiments, we tested dextromethorphan not only in a mouse model of pulmonary fibrosis, but also in living, three-dimensional, organic human lung tissue grown in the laboratory.

"As a member of the DZL consortium, we have been able to collaborate with Thoraxclinic, a local clinic in Heidelberg, and we are now planning a phase II clinical trial to investigate whether these findings can also work in human patients," said Rainer Pepperkok, head of the EMBL group and senior author of the paper.

With further assistance from EMBL's Proteomics Core Facility, Chemcore and medicinal chemists, the scientists plan to further investigate the drug, why it works and how it works. This will hopefully identify the target of the drug on cells in the context of disease, opening the possibility of developing improved variants of the drug.

"Studying collagen trafficking is interesting in itself from a cell biology perspective, but now it also has potential implications from a disease perspective," Pepperkok said. "This is still basic research and just a first step in understanding the impact of dextromethorphan on pulmonary fibrosis. Nonetheless, this fundamental discovery does appear to offer promising therapeutic potential."

Compiled from /scitechdaily