The structural and functional role of ITIH3 in the pathophysiology of myasthenia gravis

• Applicants: Dr. Christopher Nelke; Professor Dr. Tobias Ruck
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 549557400

The aim of this project proposal is to understand the role of inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) in the pathophysiology of myasthenia gravis. In myasthenia gravis, autoantibodies against the neuromuscular junction result in an impaired transmission between muscle and nerves resulting in fatigable muscle weakness. Based on our previous studies, the protein ITIH3 demonstrates specific changes in myasthenia gravis. Here, we aim to understand the role of ITIH3 in the pathophysiology of myasthenia gravis and if it can serve as a treatment target for affected patients. We will investigate the structural role of ITIH3 at the neuromuscular junction in tissue samples from myasthenia gravis patients and controls. We will also explore potential interaction partners of ITIH3 to understand its role at the molecular level. Further, we will study the functional role of ITIH3 deficiency in an experimental model of myasthenia gravis by using a knockout model and observe the impact of ITIH3 deficiency on disease severity. Overall, this project aims to shed light on the potential role of ITIH3 and its involvement in the disease pathophysiology of myasthenia gravis. The findings may lead to a better understanding of myasthenia gravis and help identify new strategies for the treatment.

• DFG Programme: Research Grants