Inclusion Body Myositis (IBM) is a rare disease where the immune system mistakenly attacks the muscles, causing them to weaken. IBM is especially puzzling because patients don’t just have immune-related muscle damage – they also develop unusual protein clumps in their muscles. These same protein build ups are seen in brain diseases like ALS and some types of dementia, which is why IBM is sometimes unclear whether it’s primarily a muscle or brain disease.

One possible culprit is a process called ISGylation. This is triggered by immune signals similar to interferon, and it’s already known to cause protein problems called TDP-43 and p62 in brain tissue. Our research will explore whether this same process is also happening in IBM-affected muscle. By comparing IBM muscle tissue to other muscle diseases and healthy tissue, we hope to understand better what drives this protein buildup—and potentially find new ways to treat it.