MYA-IN-DEPTH: Myasthenia gravis - In depth-characterization of antibody-specific pathomechanisms at the neuromuscular junction and identification of novel autoantibodies

Study Description:
Myasthenia gravis (MG) is a rare autoimmune disease that leads to a disturbance in the transmission of signals from motor nerves to muscles with the cardinal symptom of exercise-dependent muscle weakness. The cause of the disease is the formation of autoantibodies against protein molecules that are crucial for the transmission of signals at the neuromuscular junction.

The vast majority of myasthenia patients (approx. 80%) has autoantibodies against the acetylcholine receptor (AChR-ab). Other autoantibodies detected to date are directed against muscle-specific kinase (MuSK, approx. 3%) and lipoprotein-related protein 4 (LRP4, approx. 2%). Approximately, 15% of MG patients are termed “seronegative” (SNMG), meaning that no known serum antibodies can be detected.

Seronegative MG patients are significantly underrepresented in medical research, as most therapeutic approaches are aimed exclusively at treating patients with acetylcholine receptor antibodies. The aim of the MYA-IN-DEPTH study is to better understand the antibody-specific molecular and cellular immune mechanisms that contribute to the development and course of myasthenia gravis. We use blood and skeletal muscle samples to investigate similarities and differences in MG patients depending on their antibody status with the aim ofidentifying diagnostic, prognostic and therapy response markers in MG and to, ultimately,develop novel antibody-specific therapeutic approaches. In addition, this research project aims to identify novel autoantibodies against postsynaptic epitopes in currently seronegative MG patients.

Principal investigator: Dr. med. Sarah Hoffmann (Charité – Universitätsmedizin Berlin, Department of Neurology with Experimental Neurology)

Registration: The study is registered in DRKS-ID (DRKS00025711)

Course of the study: 09/2021