Agonist antibody to MuSK protects mice from MuSK myasthenia gravis

被引：1

作者：

Oury, Julien ^{[1
,6
]}

Gamallo-Lana, Begona ^{[2
]}

Santana, Leah ^{[1
,2
]}

Steyaert, Christophe

Vergoossen, Dana L. E.

Mar, Adam C.

Vankerckhoven, Bernhardt ^{[3
]}

Silence, Karen ^{[3
]}

Vanhauwaert, Roeland ^{[3
]}

Huijbers, Maartje G. ^{[4
,5
]}

Burden, Steven J. ^{[1
,7
]}

机构：

[1] NYU, Skirball Inst, Helen L & Martin S Kimmel Ctr Biol & Med, Med Sch, New York, NY 10016 USA

[2] NYU, Neurosci Inst, Sch Med, Dept Neurosci & Physiol, New York, NY 10016 USA

[3] Argenx, B-9052 Zwijnaarde, Belgium

[4] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RC Leiden, Netherlands

[5] Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RC Leiden, Netherlands

[6] Tevard Biosci, Cambridge, MA 02142 USA

[7] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2024年 / 121卷 / 39期

关键词：

autoimmune disease; myasthenia gravis; therapeutic antibody; neuromuscular; synapse; NEUROMUSCULAR-JUNCTION FORMATION; TYROSINE KINASE MUSK; RECEPTOR; LRP4; AGRIN; AUTOANTIBODIES; DOMAIN; MODELS; FORMS;

D O I：

10.1073/pnas.2408324121

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Myasthenia gravis (MG) is a chronic and severe disease of the skeletal neuromuscular junction (NMJ) in which the effects of neurotransmitters are attenuated, leading to muscle weakness. In the most common forms of autoimmune MG, antibodies attack components of the postsynaptic membrane, including the acetylcholine receptor (AChR) or with the low- density lipoprotein- related receptor 4 (Lrp4) to form the signaling receptor for neuronal Agrin, a nerve- derived synaptic organizer. Pathogenic antibodies to MuSK interfere with binding between MuSK and Lrp4, inhibiting the differentiation and maintenance of the NMJ. MuSK MG can be debilitating and refractory to treatments that are effective for AChR MG. We show here that recombinant antibodies, derived from MuSK MG patients, cause severe neuromuscular disease in mice. The disease can be prevented by a MuSK agonist antibody, presented either prophylactically or after disease onset. These findings suggest a therapeutic alternative to generalized immunosuppression for treating MuSK MG by selectively and directly targeting the disease mechanism.

引用

页数：9

共 41 条

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