Journal article

Pyridostigmine but not 3,4-diaminopyridine exacerbates ACh receptor loss and myasthenia induced in mice by muscle-specific kinase autoantibody

Marco Morsch, Stephen W Reddel, Nazanin Ghazanfari, Klaus V Toyka, William D Phillips

JOURNAL OF PHYSIOLOGY-LONDON | WILEY | Published : 2013

Abstract

In myasthenia gravis, the neuromuscular junction is impaired by the antibody-mediated loss of postsynaptic acetylcholine receptors (AChRs). Muscle weakness can be improved upon treatment with pyridostigmine, a cholinesterase inhibitor, or with 3,4-diaminopyridine, which increases the release of ACh quanta. The clinical efficacy of pyridostigmine is in doubt for certain forms of myasthenia. Here we formally examined the effects of these compounds in the antibody-induced mouse model of anti-muscle-specific kinase (MuSK) myasthenia gravis. Mice received 14 daily injections of IgG from patients with anti-MuSK myasthenia gravis. This caused reductions in postsynaptic AChR densities and in endplat..

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Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

We thank the Bosch Institute's Drs Louise Cole (Advanced Microscopy Facility) and Donna Lai (Molecular Biology Facility) as well as Drs Haydn Allbutt, Graham Robertson, Dario Protti and Vladimir Balcar for technical advice. We also thank the apheresis team, Sr Beth Newman, the molecular medicine laboratory at Concord Hospital, Louise Wienholt and patients from around Australia who contributed their plasma to this research. This work was supported by the National Health and Medical Research Council (570930 to W. D. P. and S. W. R.); the Brain Foundation; and Australian Myasthenic Association in New South Wales. K. V. T was supported by a research grant from the University of Wurzburg, Germany.