Even without drinking alcohol, a non-alcoholic fatty liver disease drug was first released at the end of last year. As the second new drug development begins, corporations worldwide have jumped in, and domestic researchers have developed a new analytical technique to assist in evaluating the efficacy of the new drug.
Fatty liver disease is divided into alcoholic fatty liver due to excessive drinking and non-alcoholic fatty liver, which is related to metabolic diseases such as obesity, diabetes, and hypertension. The prevalence of non-alcoholic fatty liver is steadily increasing due to Westernized eating habits and a lack of exercise. When fat accumulates in liver cells, they become soft, and excessive production of fibrous substances like collagen can eventually lead to liver cirrhosis and liver cancer. Since the non-alcoholic fatty liver drug rezafungin developed by Madrigal Pharmaceuticals received approval from the U.S. Food and Drug Administration (FDA) in March last year, corporations globally are targeting the development of a second new drug.
The Korea Research Institute of Chemical Technology noted on the 16th that a team led by researchers Kim Hyun-woo and Bae Myung-ae developed a NANO-based analytical technique that can measure the strength of specific areas of tissue from organoids (mini organs) created from non-alcoholic fatty liver disease states while they are alive. The research results were published in December last year in the international journal ACS Biomaterials Science and Engineering.
Developing new drugs for liver disease requires measuring and analyzing responses after introducing drug candidates into fatty liver organoids. Previously, the hardness of liver tissue was measured by crushing the entire organoid, which would destroy it. The conventional chemical treatments for fixation made it impossible to measure while the organoid remained alive, making it challenging to obtain localized hardness information.
The research team developed a calculation formula to analyze measurements by selectively applying narrow pressure with NANO-sized micro forces. This method allows for measuring localized hardness without destroying the organoids.
The research team first stained the organoids with fluorescent dyes so that strong light would come from areas where fat accumulated. They found the fatty areas and applied micro-pressure with small NANO probe stick forms.
The degree to which the NANO probe bent when pressing the organoid was precisely measured through laser reflections from the probe's surface. When the measurement results were inputted into the calculation formula developed by the research team, quantifying changes in hardness due to fat accumulation became possible.
Importantly, the NANO probe analytical technique developed by the research team was conducted while keeping the organoids alive. Additionally, it applied pressure at a shallow depth of 5 micrometers, reducing liver tissue damage.
According to the research team, applying the NANO probe hardness measurement technique to non-alcoholic fatty liver organoids confirmed that the hardness of the fatty areas emitting strong fluorescent light was about 35% softer than that of areas emitting weak fluorescent light. They accurately identified where fat accumulated. The total measurement time was shortened by more than half compared to conventional methods, and the survival rate of liver cells after measurement was maintained at over 97%.
The research team plans to develop a drug efficacy evaluation technique that allows for continuous measurements of the progression of liver disease without damaging a single organoid. Lee Young-guk, the director of the Korea Research Institute of Chemical Technology, said, 'This technology developed by the research team is expected to be widely applicable not only in the development of new drugs for liver diseases but also for other diseases.'
References
ACS Biomaterials Science & Engineering (2024), DOI: https://doi.org/10.1021/acsbiomaterials.4c01242