Aptamer binding and neutralization of β1-adrenoceptor autoantibodies: basics and a vision of its future in cardiomyopathy treatment.
Autoantibodies directed against the second extracellular receptor loop of the β(1) receptor (β(1)-ECII-AABs) that belong to the superfamily of G protein-coupled receptors have been frequently found in patients with idiopathic dilated cardiomyopathy, Chagas' cardiomyopathy, and peripartum cardiomyopathy and have been clearly evidenced to be related to disease pathogenesis. Consequently, specific proteins or peptides used as binders in immunoapheresis or as in vivo neutralizers of β(1)-ECII-AABs have been suggested for patient treatment. Aptamers, which are target specifically selected short single- or double-stranded RNA or DNA sequences, are a recently introduced new molecule class applicable to bind and neutralize diverse molecule species, including antibodies. This article reviews selection technologies and characteristics of aptamers with respect to a single-stranded DNA aptamer recently identified as having a very high affinity against β(1)-ECII-AABs. The potential of this aptamer for the elimination of β(1)-ECII-AABs and in vivo neutralization is critically analyzed in view of its potential for future use in cardiomyopathy treatment.
Pathobiochemie und Medizinische Chemie, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
Annekathrin
A
Haberland
Gerd
G
Wallukat
Ingolf
I
Schimke
D058671:Adrenergic beta-1 Receptor Antagonists / Q000627:therapeutic use; D000818:Animals; D052157:Aptamers, Nucleotide / Q000378:metabolism* / Q000627:therapeutic use; D001323:Autoantibodies / Q000187:drug effects / Q000276:immunology*; D001781:Blood Component Removal; D009202:Cardiomyopathies / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D006801:Humans; D051379:Mice; D011485:Protein Binding; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000276:immunology*
D058671:Adrenergic beta-1 Receptor Antagonists; D052157:Aptamers, Nucleotide; D001323:Autoantibodies; D018342:Receptors, Adrenergic, beta-1