Professor Young-Jae Moon's team (Department of Biochemistry and Molecular Biology, School of Medicine; Department of Orthopedic Surgery, Jeonbuk National University Hospital) identified an imaging marker that can detect early signs of a rare, refractory muscle disease and proposed a new potential therapy to suppress muscle degeneration. Noting that changes begin in the muscles that support the spine before damage in the leg muscles becomes evident, they found leads for both early diagnosis and therapeutic target discovery.

The Moon team, through a multi-institutional collaboration with domestic and international researchers, confirmed early fatty infiltration of spinal muscles associated with limb-girdle muscular dystrophy type 2B/R2 and elucidated the cells and signaling pathways that drive this process. The findings were published in EMBO Molecular Medicine, a journal in molecular medicine and translational research published by the European Molecular Biology Organization (EMBO).

Limb-girdle muscular dystrophy type 2B/R2 is a rare muscle disorder in which muscles gradually weaken, causing walking difficulties and, as the disease progresses, potential reliance on a wheelchair. Because the detailed mechanisms underlying muscle damage progression have not been fully clarified, it has been difficult to identify the disease course early and to develop strategies to halt progression.

The research team focused on changes that occur in the muscles supporting the spine prior to those in the leg muscles. Observations of the research model using magnetic resonance imaging (MRI) revealed that certain spinal muscles were replaced by fat before pronounced damage appeared in the thigh muscles.

These changes also led to abnormalities in gait balance and stride. This suggests that fatty infiltration of spinal muscles may be an early sign of the disease and a potential imaging indicator for monitoring changes in gait function.

The team traced the cause of the imaging-detected changes at the cellular level. They found that fibro-adipogenic progenitor cells, which normally assist muscle regeneration, are involved in intramuscular fat accumulation. Dysregulation of the chemical signaling pathway that controls the function of these cells (the Wnt signaling pathway) caused them to favor adipose tissue formation rather than supporting muscle regeneration.

Based on this, the researchers modulated the pathway using a GSK3 inhibitor. As a result, fat accumulation was suppressed in both the spinal muscles and the damaged leg muscles of the research model. The result points to therapeutic targets and the possibility of drug development that can intervene in the process by which muscle is replaced by fat.

Professor Moon said, "This study indicates that spinal muscle MRI can capture early changes in rare muscle diseases and be used to track disease progression. Importantly, by linking observable imaging changes to the cellular and molecular mechanisms that cause them, we have laid a research foundation that goes beyond identifying early diagnostic markers to enable development of targeted therapies."

Meanwhile, this achievement was realized through a multi-center international collaboration involving Professor Tae-Sik Ko of the Department of Orthopedic Surgery, Pusan National University Hospital; Professor Ji-Hong Min of the Department of Rehabilitation Medicine, Yangsan Pusan National University Hospital; Professor Tanya Stojkovic of Sorbonne University, France; and the team led by Professor Jyoti K. Jaiswal of Children's National Research Institute and George Washington University, USA.

The research was conducted with support from the Research-Centered Hospital R&D Project of the Korea Health Industry Development Institute, the Early-Career Researcher Support Program of the Ministry of Science and ICT, and the Future Medical Research Center Development Project within the Bio·Medical Technology Development Program.