Document Detail


In vitro characterization of an acetylcholine receptor-transferrin fusion protein for the treatment of myasthenia gravis.
MedLine Citation:
PMID:  20402568     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
SHG2210, a fusion protein containing the N-terminus of human nicotinic acetylcholine receptor α (AchR-α; aa1-210) and human transferrin (TF), was characterized as a potential therapeutic for myasthenia gravis (MG) caused predominately by α subunit autoantibodies. SHG2210 was shown to be able to bind to α subunit autoantibodies and the TF receptor (TFR). SHG2210 and SHG2210-anti-AchR antibody complex are internalized through TFR-mediated endocytosis. The SHG2210 and SHG2210-anti-AchR antibody complex is present in Lamp1-positive lysosomal compartments after internalization; however, neither SHG2210 nor SHG2210-antibody complex is present in Rab11-positive recycling endosomes. SHG2210 bound to α subunit of AChR autoantibodies may be cleared by the lysosome, resulting in short cellular half-life relative to SHG2210. 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 effective therapeutic for treating MG.
Authors:
Dennis Keefe; Chuenlei Parng; Dianna Lundberg; Satyajit Ray; Jennifer Martineau-Bosco; Charan Leng; Socrates Tzartos; Jan Powell; Michael Concino; Michael Heartlein; Justin Lamsa; Serene Josiah
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Publication Detail:
Type:  Journal Article     Date:  2010-04-19
Journal Detail:
Title:  Autoimmunity     Volume:  43     ISSN:  1607-842X     ISO Abbreviation:  Autoimmunity     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8900070     Medline TA:  Autoimmunity     Country:  England    
Other Details:
Languages:  eng     Pagination:  628-39     Citation Subset:  IM    
Affiliation:
Department of Research, Shire Human Genetic Therapies, Lexington, MA 02421, USA. dkeefe@shire.com
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