title: Aptamer BC007 for neutralization of pathogenic autoantibodies directed against G-protein coupled receptors: A vision of future treatment of patients with cardiomyopathies and positivity for those autoantibodies.
abstract: Cardiomyopathies such as idiopathic dilated cardiomyopathy (DCM), Chagas' cardiomyopathy and Peripartum cardiomyopathy present with autoantibodies against G-protein coupled receptors (GPCR-AABs) that agonistically activate their receptors. For the treatment of "agonistic autoantibody diseases" and in particular DCM, the removal of the GPCR-AABs by immunoadsorption (IA) has been studied with convincing patient benefit. To overcome cost and logistics problems of IA, the application of the aptamer BC007 for in vivo neutralization of GPCR-AABs could help. We demonstrate here, that the aptamer neutralized, in vitro, the presently known cardiovascular-pathogenic GPCR-AABs. In spontaneously hypertensive rats, the aptamer demonstrated its GPCR-AAB neutralizing potency in vivo. In the serum of DCM patients, the same GPCR-AAB reduction was achieved when patients were either immunoadsorbed or patient's serum was ex vivo treated with the aptamer. In our view, aptamer BC007 treatment in GPCR-AAB-positive patients would have a comparable benefit as that seen after IA. Not knowing all that interfering with our idea of aptamer-dependent neutralization of GPCR-AABs, the first preliminary steps have been taken for bringing the idea closer to patients.
authors.affiliation: Berlin Cures GmbH, Berlin, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Wallukat
authors.affiliation: Berlin Cures GmbH, Berlin, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Müller
authors.affiliation: Berlin Cures GmbH, Berlin, Germany.
authors.forename: Annekathrin
authors.initials: A
authors.lastname: Haberland
authors.affiliation: Institut für Diabetes 'Gerhardt Katsch', Karlsburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Berg
authors.affiliation: Institut für Klinische Pharmakologie und Toxikologie, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Schulz
authors.affiliation: Institut für Diabetes 'Gerhardt Katsch', Karlsburg, Germany.
authors.forename: Ernst-Joachim
authors.initials: EJ
authors.lastname: Freyse
authors.affiliation: Institut für Klinische Pharmakologie und Toxikologie, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Vetter
authors.affiliation: Institut für Diabetes 'Gerhardt Katsch', Karlsburg, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Salzsieder
authors.affiliation: Institut für Klinische Pharmakologie und Toxikologie, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kreutz
authors.affiliation: Berlin Cures GmbH, Berlin, Germany. Electronic address: schimke@berlincures.de.
authors.forename: Ingolf
authors.initials: I
authors.lastname: Schimke
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D052157:Aptamers, Nucleotide / Q000494:pharmacology*; D001323:Autoantibodies / Q000276:immunology*; D001781:Blood Component Removal / Q000379:methods*; D009202:Cardiomyopathies / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D002478:Cells, Cultured; D004195:Disease Models, Animal; D032383:Myocytes, Cardiac / Q000276:immunology* / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D043562:Receptors, G-Protein-Coupled / Q000276:immunology* / Q000378:metabolism
chemical_list: D052157:Aptamers, Nucleotide; D001323:Autoantibodies; D043562:Receptors, G-Protein-Coupled
keywords: Aptamer; Autoantibodies; Beta1-adrenergic receptor; Cardiomyopathy; G-protein coupled receptor