Exosome-based combination therapy shows promise for treatment of metabolically challenging disease MASH

DGIST Department of New Biology Professor Yea Kyungmoo and his research team have developed a next-generation exosome-based drug-delivery technology to effectively treat metabolic dysfunction-associated steatohepatitis (MASH), an incurable metabolic disease, in collaboration with Professor Baek Moon-chang of Kyungpook National University School of Medicine.

The paper is published in the journal Biomaterials.

MASH is a complex disease that accompanies various metabolic diseases, such as obesity and diabetes, and existing therapies are limited in their effectiveness since they target only a single pathological mechanism. Some candidates have either failed clinical trials or are delayed in approval due to cardiovascular side effects or long-term use concerns. Such circumstances demonstrate the need for safer and more effective combination treatment strategies.

To address these challenges, Professor Yea’s research team achieved the simultaneous engineering of the interior and the surface of extracellular vesicles (exosomes), biologically derived particles that play a vital role in delivering signals between cells, to formulate a bifunctional drug-delivery system that is specific to the treatment of pathologically complex MASH.

Exosomes, which carry various molecules including proteins, lipids, and genetic materials, are produced naturally in the body and are considered a promising next-generation drug-delivery system because they have higher biocompatibility, lower toxicity, and fewer side effects than existing lipid-based drug-delivery systems (such as COVID-19 vaccines).

The research is designed to regulate metabolic abnormalities, inflammation, and fibrosis simultaneously, the main pathological mechanisms of MASH, by attaching the potent fat-burning protein Fibroblast Growth Factor 21 (FGF21) to the surface of the exosomes, and enclosing miRNA-223, which is effective for regulating inflammation and fibrosis. In particular, the exosomes may be delivered explicitly to liver tissues, maximizing treatment efficiency.

“This research is the first to demonstrate a novel combination treatment concept utilizing exosomes for MASH, a metabolic disease that is difficult to treat. It sheds light on the potential to overcome the limitations of existing treatment strategies,” Professor Yea said. “We hope to establish a mass production system in the future that will lead to actual drug development.”