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.