Author + information
- Gerd Wallukat, PhD,
- Annekathrin Haberland, PhD and
- Ingolf Schimke, PhD∗ ()
- ↵∗Medizinische Chemie und Pathobiochemie, Charité–Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
We read the state-of-the-art paper by Nunes et al. (1), which presents the current knowledge on Chagas disease. For counteracting Chagas heart disease, the most life-threatening complication in chronic Chagas patients, the authors stated that “…management… followed… recommendations for… heart failure due to other conditions” (1), which includes the prevention of thromboembolism, arrhythmia, dysautonomia, and ventricular dysfunction.
As mentioned by the authors, there are agonistic autoantibodies against G-protein coupled receptors (GPCR-AABs), such as those against the muscarinergic-2 receptor (M2-AABs) and the beta1-adrenergic receptor (beta1-AABs), which are found in nearly all Chagas heart patients. M2-AABs are thought to contribute to patients’ dysautonomia, whereas beta1-AABs are seen as drivers of cardiomyopathy. Consequently, to counteract the pathogenic potency of beta1-AABs, but presently only directed to beta1-AAB–positive patients with idiopathic dilated cardiomyopathy, new treatment strategies are under study that focus on beta1-AAB removal via an apheresis technique or drug treatment for in vivo beta1-AAB neutralization (2). However, both strategies could also be helpful for Chagas patients.
In beta1-AAB apheresis technology, aptamers, a new class of binders (in addition to peptides and proteins, the typical binders) and specifically, the recently identified beta1-AAB-binding aptamer, which was successfully tested in apheresis in animals (3), could be introduced. Due to the dual presence of beta1- and M2-AABs in Chagas heart patients, apheresis techniques that remove both GPCR-AABs in parallel, either by whole immunoglobulin G apheresis or using a column carrying our recently patented aptamer (4), which binds to the majority of cardiotropic GPCR-AABs, among which are M2- and beta1-AABs, should be optimal. However, the high costs and logistic problems of apheresis limit its application for the millions of Chagas heart patients. To overcome this, a treatment strategy using in vivo neutralization of GPCR-AABs would be, in view of costs and logistics, optimal. In view of “…excellent characteristics for systemic…administration application…” (5) of aptamers in general and combined with the evidenced neutralizing function of our GPCR-AAB-binding aptamer (4), we suggest that this molecule could be suitable for developing an innovative therapy for patients with Chagas heart disease.
- American College of Cardiology Foundation
- Nunes M.C.,
- Dones W.,
- Morillo C.A.,
- Encina J.J.,
- Ribeiro A.L.,
- for the Council on Chagas Disease of the Interamerican Society of Cardiology
- Schimke I.,
- Haberland A.,
- Wallukat G.,
- inventors; Charité–Universitätsmedizin Berlin, Max-Delbrück-Centrum für Molekulare Medizin, assignee