Researchers from The Hong Kong Polytechnic University (PolyU) and The Chinese University of Hong Kong (CUHK) have reported a ground-breaking drug discovery in treating multiple metabolic diseases related to obesity and insulin resistance like diabetes and fatty liver disease. The new drug, ABarginase, opens a new path for safe, long-lasting cures to multiple obesity related diseases simultaneously through an ingenious treatment mechanism—arginine starvation. Currently, patients often have to take multiple medications for these inter-related diseases, and are hence more prone to the potential risks of polypharmacy.
The research was led by Professors Thomas Leung Yun-chung (Professor of the Department of Applied Biology and Chemical Technology), Lo Ka Chung (Charitable Foundation Professor in Pharmaceutical Sciences of PolyU) and Alisa Shum Sau-wun, Associate Professor, School of Biomedical Sciences of the Faculty of Medicine of CUHK.
The PolyU-CUHK research team discovered that a low level of arginine (a semi-essential amino acid) in the blood can suppress fat synthesis, promote fat breakdown and sensitize cells to insulin. Native arginase can break down arginine, but it has a short circulatory half-life of less than 30 minutes.
"By using an advanced fusion protein strategy, our research team developed a long-lasting recombinant human arginase, ABarginase, that contains an albumin-binding domain, which enables it to bind with the stable and abundant albumin in the blood stream to extend its half-life by about 200-fold,” explained Leung. “ABarginase exhibits strong catabolic activity and it would only require one dose of ABarginase a week to maintain circulating arginine at low levels to achieve arginine starvation."
In preclinical studies, diet-induced obese mice were injected with ABarginase once a week, while control mice were injected with saline. Researchers found that within eight weeks of treatment with ABarginase, the treatment group's body weight, fat mass, fatty liver and characteristic features of diabetes such as high blood glucose, insulin resistance and glucose intolerance were entirely reversed.
"The promising results show that ABarginase has great potential in safely and effectively treating multiple metabolic diseases related to obesity, insulin resistance, diabetes, and most importantly nonalcoholic fatty liver disease, which has no FDA-approved drug so far. We may have found the one drug that can cure them all,” added Shum.
According to the researchers the fabrication process of ABarginase is inexpensive and highly efficient, making it affordable and widely adoptable for clinical applications. Patent applications for this invention have been filed in multiple countries. The research team is now scaling up the production for manufacturing ABarginase at Good Manufacturing Practices (GMP) grade in preparation for conducting clinical trials.