Neurol Neuroimmunol Neuroinflamm 2020 01 12;7(1). Epub 2019 Dec 12.
From the Department of Clinical Neurosciences (S.H., M.C., M.W., P.M.R.C., J.C., D.B., A.V.), Weatherall Institute of Molecular Medicine and Nuffield, University of Oxford, UK; Department of Clinical and Experimental Medicine (A.D.R., M.M., R.R.), Neurology Unit, Pisa; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.
Objective: To determine whether an SRC homology 2 domain-containing phosphotyrosine phosphatase 2 (SHP2) inhibitor would increase muscle-specific kinase (MuSK) phosphorylation and override the inhibitory effect of MuSK-antibodies (Abs).
Methods: The effect of the SHP2 inhibitor NSC-87877 on MuSK phosphorylation and AChR clustering was tested in C2C12 myotubes with 31 MuSK-myasthenia gravis (MG) sera and purified MuSK-MG IgG4 preparations.
Results: In the absence of MuSK-MG Abs, NSC-87877 increased MuSK phosphorylation and the number of AChR clusters in C2C12 myotubes in vitro and in DOK7-overexpressing C2C12 myotubes that form spontaneous AChR clusters. Read More