Injection of a soluble fragment of neural agrin (NT-1654) considerably improves the muscle pathology caused by the disassembly of the neuromuscular junction
Treatment of neuromuscular diseases is still an unsolved problem. Evidence over the last years strongly indicates the involvement of malformation and dysfunction of neuromuscular junctions in the development of such medical conditions. Stabilization of NMJs thus seems to be a promising approach to a...
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Published in | PloS one Vol. 9; no. 2; p. e88739 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
10.02.2014
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | Treatment of neuromuscular diseases is still an unsolved problem. Evidence over the last years strongly indicates the involvement of malformation and dysfunction of neuromuscular junctions in the development of such medical conditions. Stabilization of NMJs thus seems to be a promising approach to attenuate the disease progression of muscle wasting diseases. An important pathway for the formation and maintenance of NMJs is the agrin/Lrp4/MuSK pathway. Here we demonstrate that the agrin biologic NT-1654 is capable of activating the agrin/Lrp4/MuSK system in vivo, leading to an almost full reversal of the sarcopenia-like phenotype in neurotrypsin-overexpressing (SARCO) mice. We also show that injection of NT-1654 accelerates muscle re-innervation after nerve crush. This report demonstrates that a systemically administered agrin fragment has the potential to counteract the symptoms of neuromuscular disorders. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: SH RGF MAR JWV. Performed the experiments: SH SL SK MH FO. Analyzed the data: SH SL SK MH FO MAR JWV. Contributed reagents/materials/analysis tools: SH SL SK MH FO. Wrote the paper: SH SL RGF MAR JWV. Competing Interests: The authors have the following interests. Stefan Hettwer, Stefan Kucsera, Monika Haubitz, Ruggero G. Fariello and Jan W. Vrijbloed are employed by Neurotune AG, and Stefan Hettwer, Ruggero G. Fariello and Jan W. Vrijbloed are shareholders of Neurotune. Neurotune is owned by shareholders and has interests to develop NT-1654 further to clinical applications. A patent application (PCT/EP2010/005372; US2012/0208765 A1) is pending with the title: “Modified agrin fragment capable of restoring muscle strength for use as a medicament”. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0088739 |