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

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 beta(1)-adrenoceptor and the muscarinic M-2-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 beta(1)-adrenoceptor specific autoantibodies and also the occurrence of further autoantibodies of this class such as the ones against the beta(2)- and alpha(1)-adrenoceptor, the ETA1-, proteinase activated-, and the AT(1)-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 Bt 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. (C) 2016 Elsevier B.V. All rights reserved.