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3rd Global Summit on Heart Diseases

Bangkok, Thailand

Ingolf Schimke

Ingolf Schimke

Berlin Cures GmbH, Berlin

Title: The aptamer BC 007 for in vivo neutralization of pathogenic autoantibodies directed against G-protein coupled receptors present in patients with cardiomyopathy: Steps to a new treatment option


Biography: Ingolf Schimke


With the finding of autoantibodies directed against G-protein coupled receptors (GPCR-AABs) in diseased subjects – mainly those suffering from diseases of the cardiovascular system – a new class of autoimmune diseases (functional autoantibody disease) has been introduced. While autoantibodies in the classic autoimmune diseases play a role in the destruction of their targets and target tissues, GPCR-AABs are so-called “functional autoantibodies” that mainly activate agonistically their related receptors in a similar way to physiologic agonists. However, receptor down regulation and desensitization for controlling of over-boarding effects of physiologic agonists are lacking for GPCR-AABs. Patients suffering from cardiomyopathies such as idiopathic dilated cardiomyopathy (DCM), Chagas’ cardiomyopathy and Peripartum cardiomyopathy present with autoantibodies against G-protein coupled receptors (GPCR-AABs) mainly such directed against the beta1-adrenergic receptor (beta1-AABs) which are clearly evidenced as driving the pathogenesis. For the treatment of “functional autoantibody disease” and in particular of DCM, the removal of the beta1-AABs by immunoadsorption (IA) has been studied with convincing patient benefit. To overcome cost and logistics problems of IA, the application of the aptamer BC 007 (single short DNA molecule for highly-specific binding of GPCR-AABs) for in vivo neutralization of beta1-AABs could help. BC 007 neutralized in vitro beta1-AABs prepared from cardiomyopathy patients as well as other GPCR-AABs present in cardiomyopathy patients who additionally suffering for example from metabolic syndrome, hypertension or diabetes mellitus. The aptamer’s in vivo beta1-AAB neutralizing potency was demonstrated in animals and recently for the first time in a beta1-AAB positive human. Due to BC 007’s safety, demonstrated in pre-clinical studies and phase 1 clinical trial, BC 007 treatment of beta1-AAB positive cardiomyopathy patients would, in our view, have a comparable benefit as that was seen after IA. Consequently, steps have been taken for bringing BC 007 as a drug for in vivo neutralization of GPCR-AABs closer to patients.