Researchers at NTHU and NHRI Develop New Drug for Treating Chronic Intestinal Inflammation

/EIN News/ -- HSINCHU, Taiwan, March 05, 2025 (GLOBE NEWSWIRE) -- Assistant Professor Yu-Hsin Chiu (邱于芯) from National Tsing Hua University (NTHU) in Taiwan and Director Hsing-Pang Hsieh (謝興邦) of the National Health Research Institutes (NHRI) have developed a drug to treat chronic intestinal inflammation, driven by modern stress and poor diets, causing diarrhea and indigestion. By blocking ion channels on intestinal cells, this breakthrough, published in Advanced Science, offers new hope.

Inflammatory bowel disease (IBD) affects approximately 5% of the population in Western countries. Statistics from Taiwan's National Health Insurance Administration reveals that in 2022 the prevalence of ulcerative colitis was 19.6 cases per 100,000 people, while Crohn's disease affected around 8.3 per 100,000.

Individuals with these chronic conditions often suffer from symptoms such as abdominal pain, diarrhea, and bloody stools, with severe cases potentially leading to life-threatening complications like intestinal perforation. According to Assistant Professor Yu-Hsin Chiu, bowel inflammation stems from an immune system disorder that currently has no cure. While anti-inflammatory drugs and steroids can help manage the condition, they offer only temporary relief, as the disease frequently relapses.

While recently developed biologics can help manage the symptoms of inflammatory bowel disease, their high costs place a significant financial burden on both patients and the national healthcare system. In response to this challenge, a collaborative research team from NTHU and NHRI has taken an innovative approach, developing a small-molecule drug that blocks the opening of ion channels in intestinal mucosal cells, thereby effectively reducing inflammation.

Chiu explained that when intestinal cells are damaged, they release ATP – a major source of energy in cells-- through PANX1 channels, which recruits immune cells to target and remove the damaged cells. However, in cases of inflammatory bowel disease, this pathway remains persistently active, creating a vicious cycle that exacerbates intestinal damage.

By blocking this pathway, it is possible to disrupt the inflammatory response and prevent further tissue injury. This led Chiu to consider that blocking the ion channels responsible for the release of inflammation-triggering molecules could be comparable to sealing Pandora’s box, offering a promising strategy for effectively treating chronic intestinal inflammation.

Ten years ago, Chiu worked with a research team at the University of Virginia in the United States and discovered a drug that inhibits PANX1. However, its clinical application was prohibited due to liver toxicity. In her recent research with Hsieh and Jing-Chyi Lee from NHRI, Chiu successfully modified the drug’s molecular structure, improving its efficacy while significantly reducing its toxicity.

Director Hsing-Pang Hsieh is an alumnus of NTHU, who earned both his bachelor's and master's degrees in Chemistry. He also serves as a jointly appointed professor in NTHU’s Department of Chemistry. Hsieh compared drug development to crafting the perfect key for a specific lock.

The research team, co-led by Hsieh, used chemical modifications to increase the distance of a carbon atom within the drug’s molecular structure, creating more space for three-dimensional rotation. This adjustment altered the planar structure responsible for liver toxicity, while also enhancing the drug’s efficacy.

Chiu also noted that beyond intestinal diseases, this new drug shows promising potential for treating a range of other inflammatory conditions, including stroke, epilepsy, and chronic pain. This breakthrough opens up new strategies for addressing tissue damage and immune-related disorders, paving new avenues for broader therapeutic applications.

This three-year research project was a collaborative effort involving experts from multiple disciplines. The chemical synthesis and refinement of the new drug were led by Wen-Yun Hsueh (薛雯勻), a doctoral student in NTHU’s Department of Chemistry, while Yi-Ling Wu (吳苡伶), a master’s student at the Institute of Biotechnology, conducted compound screening and activity testing.

To further validate the drug’s mechanism of action, Professor Ping-Chiang Lyu (呂平江) from the College of Life Sciences and Medicine utilized computer-aided molecular docking simulations. The research team also expressed gratitude to Dr. Meng-Tzu Weng (翁孟慈) from the Hsinchu Branch of the National Taiwan University Hospital and Dr. Shu-Chen Wei (魏淑鉁) from the National Taiwan University Hospital for their support in animal experiments, which confirmed the drug’s effectiveness in reducing intestinal inflammation.

Additionally, the project benefited from a collaboration with Professor Ivan Poon’s research team at La Trobe University in Australia, further strengthening its scientific foundation.

Contact:
Holly Hsueh
NTHU
(886)3-5162006
hoyu@mx.nthu.edu.tw

Members of the research team (left to right): Wen-Yun Hsueh (薛雯勻), doctoral student in the Department of Chemistry; Hsing-Pang Hsieh (謝興邦), director of the Institute of Biotechnology and Pharmaceutical Research at NHRI; Assistant Professor Yu-Hsin Chiu (邱于芯) of the College of Life Sciences and Medicine; and Yi-Ling Wu (吳苡伶), master's student in the Institute of Biotechnology.

(Photo: National Tsing Hua University)

A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/8989cfcf-d29e-40f4-a0b6-d8218dd05181