Biomedical Engineering Reference
In-Depth Information
12.6 CONCLUSION
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gamma and epsilon subunits of the human acetylcholine
receptor as immunoadsorbents for myasthenic autoantibodies:
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receptor-transferrin fusion protein for the treatment of myas-
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76 of the alpha subunit. Proc. Natl. Acad. Sci. USA 85(9),
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dependent epitopes on the N-terminal extracellular domain of
the human muscle acetylcholine receptor alpha subunit
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22. Beeson D, et al. (1996) A transfected human muscle cell line
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line receptor recycling and its role in maintaining receptor
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24. Bruneau EG, Akaaboune M, (2006) The dynamics of recycled
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In conclusion, in vitro studies are a valuable approach to
assessing the mechanism of action and potential efficacy of
fusion proteins: (1) SHG2210 is able to bind to
a
-subunit
autoantibodies and the TF receptor (TFR) and (2) SHG2210
and SHG2210-anti-AchR antibody complex are internalized
through TFR-mediated endocytosis. SHG2210 is shown to
have a protective effect on antigenic modulation of the
AChR induced by serum from select patients with MG,
suggesting that a fusion protein approach may be an effec-
tive therapeutic for treating MG and TF fusion proteins may
remove targeted molecules from circulation. The studies
outlined in this chapter provide an overview of the charac-
terization of a AChR-TF-specific fusion protein in the
context of a potential strategy for the treatment of myasthe-
nia gravis. Key points to consider when characterizing a TF-
based fusion protein are (1) binding properties of each
portion of the fusion protein, (2) TFR binding and uptake,
and (3) cellular trafficking. The use of TF as a fusion partner
for tissue targeting and delivery remains a promising area of
research.
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