Abstract
Autoantibodies (AABs) against the second extracellular loop of the beta1-receptor (beta1(II)-AABs) are found as a pathogenic driver in patients with idiopathic dilated cardiomyopathy, Chagas cardiomyopathy, peripartum cardiomyopathy, and myocarditis, and have been increasingly seen as a treatment target. We recently identified an aptamer (single short DNA strand) that specifically binds and neutralizes beta1(II)-AABs. Via application of this aptamer, a new treatment strategy for diseases associated with the cardio-pathogenic beta1(II)-AABs could be developed. Spontaneously hypertensive rats (SHR) positive for beta1(II)-AABs were treated five times at weekly intervals (bolus application of 2 mg/kg body weight followed by an infusion of the same amount over 20 min). SHR responded to aptamer treatment with a strong reduction in the cardio-pathogenic beta1(II)-AABs. The AABs did not substantially return within the study period. No signs for aptamer toxicity were observed by visual examination of the heart, liver, and kidney, or by measurement of plasma CK, ALT, and creatinine. The aptamer’s potential for beta1(II)-AAB neutralization and consequently for cardiomyopathy treatment has been shown for the first time in vivo.
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Acknowledgments
We are grateful to Jens Peter Teifke (Friedrich-Loeffler-Institut, Insel Riems, Germany) for providing the slide-scanning system and his support in morphometric measurements as well as to “European Regional Development Fund” (10141685), Berlin, Germany and “Stiftung Pathobiochemie der Deutschen Gesellschaft für Klinische Chemie und Laboratoriumsmedizin” (105/2011, 128/2013), Bonn, Germany for financial support.
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A. Haberland and G. Wallukat have contributed equally to this work.
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Haberland, A., Wallukat, G., Berg, S. et al. Neutralization of pathogenic beta1-receptor autoantibodies by aptamers in vivo: the first successful proof of principle in spontaneously hypertensive rats. Mol Cell Biochem 393, 177–180 (2014). https://doi.org/10.1007/s11010-014-2057-8
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DOI: https://doi.org/10.1007/s11010-014-2057-8