Targeting RBCK1 disease mechanisms

RBCK1 disease is a rare genetic condition that affects muscles, the heart and the immune system. Patients may develop muscle weakness, cardiomyopathy, repeated infections, and inflammation. A key feature of the disease is the build-up of abnormal sugar-like material, called polyglucosan bodies, inside cells, which can damage tissues. However, the exact cause of this toxic accumulation is still not fully understood. In the first RBCK1 seed project, we studied skin-derived patient fibroblast cell lines and transformed them into pluripotent stem cells. Our results showed that these models replicate important features of the disease, such as the accumulation of polyglucosan bodies and issues in how cells produce energy and manage stress. Additional findings led us also to hypothesise that several cellular processes—such as inflammation, energy production, and waste removal—are disrupted and interact in a harmful cycle that drives disease progression. To further investigate this, we will use advanced cell models, including three-dimensional “mini-tissues”, with the final goal of better understanding how RBCK1 disease develops and to identify possible treatments. At the same time, we will test compounds able to modulate inflammation and cellular energy production/stress, and we will complete the screening of drugs that are already approved for other conditions. This approach could help identify effective therapies more quickly. Overall, this research aims to improve the understanding of RBCK1 disease and support the development of new treatments. In the long term, it may lead to better care for patients and could also benefit other related muscle disorders that currently lack effective therapies.