In Vivo Effects of Antibodies Blocking Acchr Function Ion

Richman, David P.

Abstract

Our previous observation that injection of monoclonal antibodies (mAbs) that block acetylcholine receptor (AcChR) function results in an extremely severe form of """"""""hyperacute"""""""" experimental myasthenia, support the hypothesis that anti-AcChR antibodies of this type play a significant role in myasthenia gravis and experimental myasthenia. To further test this hypothesis we will assess the effect on neuromuscular transmission of members of our present library of anti-AcChR mAbs and of new anti-AcChR and anti-peptide mAbs to be developed in Project 5 and the Scientific Core. In addition we will attempt to develop a new form of treatment of experimental myasthenia consisting of injection of epitope-mimicking peptides as a form of """"""""blocking antigen"""""""". The effect of these mAbs on neuromuscular transmission and neuromuscular junction histology and biochemistry will be assessed both in vitro and in vivo. The methods to be used in this collaborative Project include clinical assessment, clinical electromyography, light and electron microscopy, intracellular endplate recordings, determination of muscle AcChR content, and serological analysis of subtypes of AcChR antibodies.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Neurological Disorders and Stroke (NINDS)
• Type: Research Program Projects (P01)
• Project #: 1P01NS024304-01
• Application #: 3946159
• Support Year: 1
• Fiscal Year: 1987

Institution

• Name: University of Chicago
• DUNS #: 225410919
• City: Chicago
• State: IL
• Country: United States
• Zip Code: 60637

Publications

Fairclough, R H; Twaddle, G M; Gudipati, E et al. (1998) Mapping the mAb 383C epitope to alpha 2(187-199) of the Torpedo acetylcholine receptor on the three-dimensional model. J Mol Biol 282:301-15

Fairclough, R H; Twaddle, G M; Gudipati, E et al. (1998) Differential surface accessibility of alpha(187-199) in the Torpedo acetylcholine receptor alpha subunits. J Mol Biol 282:317-30

Richman, D P; Agius, M A; Kirvan, C A et al. (1998) Antibody effector mechanisms in myasthenia gravis. The complement hypothesis. Ann N Y Acad Sci 841:450-65

Fairclough, R H; Gudipati, E; Lin, M Y et al. (1998) A role for alpha(187-199) in the conversion of agonist binding energy to the opening of the acetylcholine receptor ion channel. Ann N Y Acad Sci 841:87-92

Richman, D P; Agius, M A (1994) Acquired myasthenia gravis. Immunopathology. Neurol Clin 12:273-84

Richman, D P; Agius, M A (1994) Myasthenia gravis: pathogenesis and treatment. Semin Neurol 14:106-10

Fairclough, R H; Josephs, R; Richman, D P (1993) Imaging ligand binding sites on the Torpedo acetylcholine receptor. Ann N Y Acad Sci 681:113-25

Xu, Q; Agius, M; Gudipati, E et al. (1993) An immunogenic self-peptide for T cells in mice with experimental myasthenia. Ann N Y Acad Sci 681:1-4

Xu, Q; Twaddle, G M; Richman, D P et al. (1993) Characterization of the epitope of an antiacetylcholine receptor antibody that inhibits fifty percent of alpha-bungarotoxin binding. Ann N Y Acad Sci 681:175-8

Xu, Q; Fairclough, R H; Richman, D P (1993) Interaction of antiacetylcholine receptor monoclonal antibodies with the acetylcholine receptor. Ann N Y Acad Sci 681:172-4