TY - JOUR
T1 - Aptamer BC 007 – A broad spectrum neutralizer of pathogenic autoantibodies against G-protein-coupled receptors
AU - Haberland, Annekathrin
AU - Holtzhauer, Martin
AU - Schlichtiger, Alice
AU - Bartel, Sabine
AU - Schimke, Ingolf
AU - Müller, Johannes
AU - Dandel, Michael
AU - Luppa, Peter B.
AU - Wallukat, Gerd
N1 - Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Aptamer
KW - Autoantibody
KW - Dilated cardiomyopathy
KW - G-protein-coupled receptors
KW - Immunoadsorption
KW - Therapy
UR - http://www.scopus.com/inward/record.url?scp=84978372304&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2016.06.061
DO - 10.1016/j.ejphar.2016.06.061
M3 - Article
C2 - 27375076
AN - SCOPUS:84978372304
SN - 0014-2999
VL - 789
SP - 37
EP - 45
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -