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Each year, TMA awards research funding to support innovative investigations to improve understanding and treatment of myositis diseases. Dr. Thomas Lloyd recently completed such a project in which he and his team developed a new patient-derived muscle cell model to study inclusion body myositis (IBM) and explore potential new therapies. This model allows them to study how IBM develops at the cellular level and to explore whether treatments that target aging cells—called senolytic therapies—might help.
Their research focused on three main goals. First, the team wanted to identify key differences between muscle cells from IBM patients and those from healthy individuals. Second, they examined the role of cellular senescence, which is a state where cells stop dividing and begin to age in a harmful way. Third, they tested whether certain drugs could reduce or reverse these harmful changes.
The researchers found clear differences between IBM and non-IBM muscle cells at every stage of development. Muscle cells from IBM patients showed higher activity in genes linked to stress, inflammation, and muscle breakdown. Genes associated with DNA damage were also more active. This suggests that IBM muscle cells have built-in disease traits, even when studied outside the body.
Further analysis showed that IBM shares some biological pathways with neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. This points to possible common disease mechanisms.
The team also found strong evidence of ongoing DNA damage in IBM muscle cells. Proteins that signal DNA damage were more active, which can stop cells from dividing and push them toward aging. Normally, healthy cells can repair this damage. However, IBM cells had lower levels of important DNA repair proteins. Interestingly, the genes that produce these proteins were still working normally, suggesting the problem may lie in how the proteins are handled inside the cell.
In addition, IBM muscle cells produced higher levels of inflammatory substances, a pattern known as the “senescence-associated secretory phenotype” (SASP). These substances, including interleukins, can worsen inflammation and may help drive disease progression. Altogether, these findings support the idea that aging cells and poor DNA repair play a key role in IBM.
In the final part of the study, researchers tested two senolytic drugs, dasatinib and quercetin, to see if they could improve the condition of IBM muscle cells. After selecting safe doses, they treated the cells with these drugs. The treatment did not significantly reduce signs of aging or inflammation, though. This result suggests that these drugs may not work in this model, or that different treatment conditions are needed. The researchers noted that more complex studies, such as those using animal models, may provide clearer answers.
Even so, this study marks an important step forward. Creating a reliable model based on patient cells is a major achievement. It allows scientists to study IBM in a controlled setting that closely reflects what happens in patients. The model also shows key features seen in real muscle tissue, including inflammation, muscle damage, and abnormal protein behavior.
Overall, the study shows that IBM muscle cells are inherently abnormal. They have higher levels of inflammation, DNA damage, and signs of early aging, along with weakened repair systems. These findings suggest new directions for treatment, especially approaches that target DNA damage or aging cells. Although the tested senolytic drugs were not effective, the results will help guide future research.
“I’m excited that our data show very clear IBM-related features in this new laboratory model,” Dr. Lloyd said. “It suggests this can be a useful tool for studying how IBM develops and for testing new treatments.”
Dr. Lloyd is a former member of TMA’s Medical Advisory Board. He is a Professor of Medicine and Chair of the Department of Neurology at Baylor College of Medicine in Houston, Texas.
