IMMUNOTHERAPY OF EXPERIMNTL AUTOIMMUNE MYASTHENIA GRAVIS

Project: Research project

Project Details

Description

Myasthenia gravis (MG) is an autoimmune disease in which neuromuscular
transmission is impaired, probably due to circulating antibodies directed
against the acetylcholine receptor (AChR) found in the postsynaptic
membrane of the neuromuscular junction. Injection of purified AChR into
rats produces chronic symptoms very similar to those demonstrated by MG
patients. The goal of this project is to develop a successful
immunotherapeutic approach to the treatment of MG using the rat model,
experimental autoimmune myasthenia gravis (EAMG). Emphasis will be on the
elimination of the clones of lymphocytes capable of reacting with the AChR
by treatment with synthetic hybrid toxins composed of the active peptide of
the toxin, ricin, covalently linked to a binding moiety which will direct
the toxin specifically to the autoreactive cells. This investigation will
be conducted at two levels: 1) Delete autoreactive clones in vitro and in
vivo by treatment with antigen coupled to the A-chain of ricin; i.e., ricin
A-chain will be covalently coupled to purified AChR which will then be used
to delete (kill) clones of B lymphocytes which express antigen receptors
and therfore reactivity for AChR, and 2) Delete autoreactive clones in
vitro and in vivo by treatment with anti-idiotypic antibodies coupled to
antibodies reactive with the clonally expressed determinants (idiotypes)
associated with the antigen binding sites of receptors on AChR-reactive B
lymphocytes, will be used to delete (kill) those AChR-specific cells. The
ultimate goal of this study is to use these specific immunotoxic agents
(perhaps in conjunction with non-specific immunosuppressive drugs) to
induce long-term remissions of EAMG symptoms demonstrated by animals with
progressive disease.
StatusFinished
Effective start/end date12/1/8311/30/90

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Neuroscience(all)

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