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- W2025101651 abstract "Muscle-specific tyrosine kinase (MuSK) autoantibodies are the hallmark of a form of myasthenia gravis (MG) that can challenge the neurologist and the experimentalist. The clinical disease can be difficult to treat effectively. MuSK autoantibodies affect the neuromuscular junction in several ways. When added to muscle cells in culture, MuSK antibodies disperse acetylcholine receptor clusters. Experimental animals actively immunized with MuSK develop MuSK autoantibodies and muscle weakness. Weakness is associated with reduced postsynaptic acetylcholine receptor numbers, reduced amplitudes of miniature endplate potentials and endplate potentials, and failure of neuromuscular transmission. Similar impairments have been found in mice injected with IgG from MG patients positive for MuSK autoantibody (MuSK-MG). The active and passive models have begun to reveal the mechanisms by which MuSK antibodies disrupt synaptic function at the neuromuscular junction, and should be valuable in developing therapies for MuSK-MG. However, translation into new and improved treatments for patients requires procedures that are not too cumbersome but suitable for examining different aspects of MuSK function and the effects of potential therapies. Study design, conduct and analysis should be carefully considered and transparently reported. Here we review what has been learnt from animal and culture models of MuSK-MG, and offer guidelines for experimental design and conduct of studies, including sample size determination, randomization, outcome parameters and precautions for objective data analysis. These principles may also be relevant to the increasing number of other antibody-mediated diseases that are now recognized." @default.
- W2025101651 created "2016-06-24" @default.
- W2025101651 creator A5002313608 @default.
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- W2025101651 creator A5071437011 @default.
- W2025101651 creator A5074297051 @default.
- W2025101651 date "2015-08-01" @default.
- W2025101651 modified "2023-10-16" @default.
- W2025101651 title "Guidelines for pre-clinical animal and cellular models of MuSK-myasthenia gravis" @default.
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- W2025101651 doi "https://doi.org/10.1016/j.expneurol.2014.12.013" @default.
- W2025101651 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25542979" @default.
- W2025101651 hasPublicationYear "2015" @default.
- W2025101651 type Work @default.