Zhiguo Li1,2, Minshu Li1,2, Kristofer Wood1, Steffan Hettwer3, Suraj A Muley1, Fu-Dong Shi1,2, Qiang Liu1,2, Shafeeq S Ladha1. 1. Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, 85013, USA. 2. Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China. 3. Neurotune AG, Schlieren-Zurich, Switzerland.
Abstract
INTRODUCTION: Agrin is essential for the formation and maintenance of neuromuscular junctions (NMJs). NT-1654 is a C-terminal fragment of mouse neural agrin. In this study, we determined the effects of NT-1654 on the severity of experimental autoimmune myasthenia gravis (EAMG). METHODS: EAMG was induced in female Lewis rats by immunization with the Torpedo acetylcholine receptor (tAChR) and complete Freund's adjuvant (CFA). NT-1654 was dissolved in phosphate-buffered saline (PBS) and injected daily subcutaneously into tAChR immunized rats during the first 10 days after immunization, and then every other day for the following 20 days. RESULTS: We showed that NT-1654 attenuated clinical severity, effectively promoted the clustering of AChRs at NMJs, and alleviated the impairment of NMJ transmission and the reduction of muscle-specific kinase (MuSK) in EAMG rats. DISCUSSION: We demonstrated that NT-1654 attenuated clinical severity, effectively promoted the clustering of AChRs at NMJs, and alleviated the impairment of NMJ transmission and the reduction of muscle-specific kinase (MuSK) in EAMG rats. Muscle Nerve 57: 814-820, 2018.
INTRODUCTION:Agrin is essential for the formation and maintenance of neuromuscular junctions (NMJs). NT-1654 is a C-terminal fragment of mouse neural agrin. In this study, we determined the effects of NT-1654 on the severity of experimental autoimmune myasthenia gravis (EAMG). METHODS:EAMG was induced in female Lewis rats by immunization with the Torpedoacetylcholine receptor (tAChR) and complete Freund's adjuvant (CFA). NT-1654 was dissolved in phosphate-buffered saline (PBS) and injected daily subcutaneously into tAChR immunized rats during the first 10 days after immunization, and then every other day for the following 20 days. RESULTS: We showed that NT-1654 attenuated clinical severity, effectively promoted the clustering of AChRs at NMJs, and alleviated the impairment of NMJ transmission and the reduction of muscle-specific kinase (MuSK) in EAMGrats. DISCUSSION: We demonstrated that NT-1654 attenuated clinical severity, effectively promoted the clustering of AChRs at NMJs, and alleviated the impairment of NMJ transmission and the reduction of muscle-specific kinase (MuSK) in EAMGrats. Muscle Nerve 57: 814-820, 2018.
Authors: Marina Boido; Elena De Amicis; Valeria Valsecchi; Marco Trevisan; Ugo Ala; Markus A Ruegg; Stefan Hettwer; Alessandro Vercelli Journal: Front Cell Neurosci Date: 2018-01-30 Impact factor: 5.505