Targeting therapy to the neuromuscular junction: Proof of concept

Linda L. Kusner; Namita Satija; Georgiana Cheng; Henry J. Kaminski

doi:10.1002/mus.24057

Targeting therapy to the neuromuscular junction: Proof of concept

Linda L. Kusner, Namita Satija, Georgiana Cheng, Henry J. Kaminski

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Introduction: The site of pathology in myasthenia gravis (MG) is the neuromuscular junction (NMJ). Our goal was to determine the ability to direct complement inhibition to the NMJ. Methods: A single-chain antibody directed against the alpha subunit of the acetylcholine receptor was synthesized (scFv-35) and coupled to decay-accelerating factor (DAF, scFv-35-DAF). scFv-35-DAF was tested in a passive model of experimentally acquired MG. Results: Administration of scFv-35-DAF to mice deficient in intrinsic complement inhibitors produced no weakness despite confirmation of its localization to the NMJ and no evidence of tissue destruction related to complement activation. Rats with experimentally acquired MG treated with scFV-35-DAF showed less weakness and a reduction of complement deposition. Conclusions: We demonstrate a method to effectively target a therapeutic agent to the NMJ.

Original language	English
Pages (from-to)	749-756
Number of pages	8
Journal	Muscle and Nerve
Volume	49
Issue number	5
DOIs	https://doi.org/10.1002/mus.24057
State	Published - May 2014
Externally published	Yes

Keywords

Acetylcholine receptor
Autoimmunity
Complement
Decay-accelerating factor
Myasthenia gravis

Access to Document

10.1002/mus.24057

Cite this

@article{809a9e8dbc8c493a9786daa187f347dd,

title = "Targeting therapy to the neuromuscular junction: Proof of concept",

abstract = "Introduction: The site of pathology in myasthenia gravis (MG) is the neuromuscular junction (NMJ). Our goal was to determine the ability to direct complement inhibition to the NMJ. Methods: A single-chain antibody directed against the alpha subunit of the acetylcholine receptor was synthesized (scFv-35) and coupled to decay-accelerating factor (DAF, scFv-35-DAF). scFv-35-DAF was tested in a passive model of experimentally acquired MG. Results: Administration of scFv-35-DAF to mice deficient in intrinsic complement inhibitors produced no weakness despite confirmation of its localization to the NMJ and no evidence of tissue destruction related to complement activation. Rats with experimentally acquired MG treated with scFV-35-DAF showed less weakness and a reduction of complement deposition. Conclusions: We demonstrate a method to effectively target a therapeutic agent to the NMJ.",

keywords = "Acetylcholine receptor, Autoimmunity, Complement, Decay-accelerating factor, Myasthenia gravis",

author = "Kusner, {Linda L.} and Namita Satija and Georgiana Cheng and Kaminski, {Henry J.}",

year = "2014",

month = may,

doi = "10.1002/mus.24057",

language = "English",

volume = "49",

pages = "749--756",

journal = "Muscle and Nerve",

issn = "0148-639X",

publisher = "John Wiley & Sons Inc.",

number = "5",

}

TY - JOUR

T1 - Targeting therapy to the neuromuscular junction

T2 - Proof of concept

AU - Kusner, Linda L.

AU - Satija, Namita

AU - Cheng, Georgiana

AU - Kaminski, Henry J.

PY - 2014/5

Y1 - 2014/5

N2 - Introduction: The site of pathology in myasthenia gravis (MG) is the neuromuscular junction (NMJ). Our goal was to determine the ability to direct complement inhibition to the NMJ. Methods: A single-chain antibody directed against the alpha subunit of the acetylcholine receptor was synthesized (scFv-35) and coupled to decay-accelerating factor (DAF, scFv-35-DAF). scFv-35-DAF was tested in a passive model of experimentally acquired MG. Results: Administration of scFv-35-DAF to mice deficient in intrinsic complement inhibitors produced no weakness despite confirmation of its localization to the NMJ and no evidence of tissue destruction related to complement activation. Rats with experimentally acquired MG treated with scFV-35-DAF showed less weakness and a reduction of complement deposition. Conclusions: We demonstrate a method to effectively target a therapeutic agent to the NMJ.

AB - Introduction: The site of pathology in myasthenia gravis (MG) is the neuromuscular junction (NMJ). Our goal was to determine the ability to direct complement inhibition to the NMJ. Methods: A single-chain antibody directed against the alpha subunit of the acetylcholine receptor was synthesized (scFv-35) and coupled to decay-accelerating factor (DAF, scFv-35-DAF). scFv-35-DAF was tested in a passive model of experimentally acquired MG. Results: Administration of scFv-35-DAF to mice deficient in intrinsic complement inhibitors produced no weakness despite confirmation of its localization to the NMJ and no evidence of tissue destruction related to complement activation. Rats with experimentally acquired MG treated with scFV-35-DAF showed less weakness and a reduction of complement deposition. Conclusions: We demonstrate a method to effectively target a therapeutic agent to the NMJ.

KW - Acetylcholine receptor

KW - Autoimmunity

KW - Complement

KW - Decay-accelerating factor

KW - Myasthenia gravis

UR - http://www.scopus.com/inward/record.url?scp=84901455544&partnerID=8YFLogxK

U2 - 10.1002/mus.24057

DO - 10.1002/mus.24057

M3 - Article

C2 - 24037951

AN - SCOPUS:84901455544

SN - 0148-639X

VL - 49

SP - 749

EP - 756

JO - Muscle and Nerve

JF - Muscle and Nerve

IS - 5

ER -

Targeting therapy to the neuromuscular junction: Proof of concept

Abstract

Keywords

Access to Document

Fingerprint

Cite this