2. Academic Validation
  3. Aptamer BC 007 - A broad spectrum neutralizer of pathogenic autoantibodies against G-protein-coupled receptors

Aptamer BC 007 - A broad spectrum neutralizer of pathogenic autoantibodies against G-protein-coupled receptors

  • Eur J Pharmacol. 2016 Oct 15:789:37-45. doi: 10.1016/j.ejphar.2016.06.061.
Annekathrin Haberland 1,  Martin Holtzhauer 2,  Alice Schlichtiger 3,  Sabine Bartel 4,  Ingolf Schimke 5,  Johannes Müller 6,  Michael Dandel 7,  Peter B Luppa 8,  Gerd Wallukat 9
Affiliations

Affiliations

  • 1 Medical Chemistry and Pathobiochemistry, Charité- Universitätsmedizin Berlin, Germany. Electronic address: [email protected].
  • 2 Human Gesellschaft für Biochemie und Diagnostica mbH, Magdeburg, Germany. Electronic address: [email protected].
  • 3 Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar der Technischen Universität München, Germany. Electronic address: [email protected].
  • 4 Max-Delbrück-Center for Molecular Medicine, Berlin-Buch, Germany. Electronic address: [email protected].
  • 5 Medical Chemistry and Pathobiochemistry, Charité- Universitätsmedizin Berlin, Germany. Electronic address: [email protected].
  • 6 Berlin Cures GmbH, Berlin, Germany. Electronic address: [email protected].
  • 7 Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Germany. Electronic address: [email protected].
  • 8 Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar der Technischen Universität München, Germany. Electronic address: [email protected].
  • 9 Max-Delbrück-Center for Molecular Medicine, Berlin-Buch, Germany. Electronic address: [email protected].
PMID: 27375076 DOI: 10.1016/j.ejphar.2016.06.061
Abstract

The effect of autoantibodies on G-protein coupled receptors in the pathogenesis of diseases, especially of the heart and vascular system, is an increasingly accepted fact today. Dilated cardiomyopathy (DCM) is the most intensively investigated pathological situation of these. With DCM, autoantibodies against the β1-adrenoceptor and the muscarinic M2-receptor have been found in high percentage of investigated patients. Immunoadsorption for autoantibody removal has already shown a long-term beneficial therapeutic effect, but has remained limited in its application because of the complexity of this method. A new easy applicable treatment strategy has, therefore, been discovered. Because of intra- and inter-loop epitope variability of the β1-adrenoceptor specific autoantibodies and also the occurrence of further autoantibodies of this class such as the ones against the β2- and α1-adrenoceptor, the ETA-, proteinase activated-, and the AT1-receptors in different pathological situations, this newly discovered broad-spectrum neutralizer of all these autoantibodies - aptamer BC 007 - is under development. The binding and neutralizing effect was investigated applying a bioassay of spontaneously beating neonatal rat cardiomyocytes and enzyme-linked immunosorbent assay (ELISA) - technology. The usefulness of aptamer BC 007 to specify column technology for the removal of serum autoantibodies was also demonstrated. The presented data suggest that aptamer BC 007 might be an appropriate molecule candidate to support future research about the meaning of G-protein-coupled receptor autoantibodies.

Keywords

Aptamer; Autoantibody; Dilated cardiomyopathy; G-protein-coupled receptors; Immunoadsorption; Therapy.

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