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Immunoadsorption for Treatment of Patients with Suspected Alzheimer Dementia and Agonistic Autoantibodies against Alpha1a-Adrenoceptor—Rationale and Design of the IMAD Pilot Study
Background: agonistic autoantibodies (agAABs) against G protein-coupled receptors (GPCR) have been linked to cardiovascular disease. In dementia patients, GPCR-agAABs against the α1- and ß2-adrenoceptors (α1AR- and ß2AR) were found at a prevalence of 50%. Elimination of agAABs by immunoadsorption (I...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356934/ https://www.ncbi.nlm.nih.gov/pubmed/32575439 http://dx.doi.org/10.3390/jcm9061919 |
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author | Stracke, Sylvia Lange, Sandra Bornmann, Sarah Kock, Holger Schulze, Lara Klinger-König, Johanna Böhm, Susanne Vogelgesang, Antje von Podewils, Felix Föel, Agnes Gross, Stefan Wenzel, Katrin Wallukat, Gerd Prüss, Harald Dressel, Alexander Kunze, Rudolf Grabe, Hans J. Langner, Sönke Dörr, Marcus |
author_facet | Stracke, Sylvia Lange, Sandra Bornmann, Sarah Kock, Holger Schulze, Lara Klinger-König, Johanna Böhm, Susanne Vogelgesang, Antje von Podewils, Felix Föel, Agnes Gross, Stefan Wenzel, Katrin Wallukat, Gerd Prüss, Harald Dressel, Alexander Kunze, Rudolf Grabe, Hans J. Langner, Sönke Dörr, Marcus |
author_sort | Stracke, Sylvia |
collection | PubMed |
description | Background: agonistic autoantibodies (agAABs) against G protein-coupled receptors (GPCR) have been linked to cardiovascular disease. In dementia patients, GPCR-agAABs against the α1- and ß2-adrenoceptors (α1AR- and ß2AR) were found at a prevalence of 50%. Elimination of agAABs by immunoadsorption (IA) was successfully applied in cardiovascular disease. The IMAD trial (Efficacy of immunoadsorption for treatment of persons with Alzheimer dementia and agonistic autoantibodies against alpha1A-adrenoceptor) investigates whether the removal of α1AR-AABs by a 5-day IA procedure has a positive effect (improvement or non-deterioration) on changes of hemodynamic, cognitive, vascular and metabolic parameters in patients with suspected Alzheimer’s clinical syndrome within a one-year follow-up period. Methods: the IMAD trial is designed as an exploratory monocentric interventional trial corresponding to a proof-of-concept phase-IIa study. If cognition capacity of eligible patients scores 19–26 in the Mini Mental State Examination (MMSE), patients are tested for the presence of agAABs by an enzyme-linked immunosorbent assay (ELISA)-based method, followed by a bioassay-based confirmation test, further screening and treatment with IA and intravenous immunoglobulin G (IgG) replacement. We aim to include 15 patients with IA/IgG and to complete follow-up data from at least 12 patients. The primary outcome parameter of the study is uncorrected mean cerebral perfusion measured in mL/min/100 gr of brain tissue determined by magnetic resonance imaging with arterial spin labeling after 12 months. Conclusion: IMAD is an important pilot study that will analyze whether the removal of α1AR-agAABs by immunoadsorption in α1AR-agAAB-positive patients with suspected Alzheimer’s clinical syndrome may slow the progression of dementia and/or may improve vascular functional parameters. |
format | Online Article Text |
id | pubmed-7356934 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73569342020-07-22 Immunoadsorption for Treatment of Patients with Suspected Alzheimer Dementia and Agonistic Autoantibodies against Alpha1a-Adrenoceptor—Rationale and Design of the IMAD Pilot Study Stracke, Sylvia Lange, Sandra Bornmann, Sarah Kock, Holger Schulze, Lara Klinger-König, Johanna Böhm, Susanne Vogelgesang, Antje von Podewils, Felix Föel, Agnes Gross, Stefan Wenzel, Katrin Wallukat, Gerd Prüss, Harald Dressel, Alexander Kunze, Rudolf Grabe, Hans J. Langner, Sönke Dörr, Marcus J Clin Med Article Background: agonistic autoantibodies (agAABs) against G protein-coupled receptors (GPCR) have been linked to cardiovascular disease. In dementia patients, GPCR-agAABs against the α1- and ß2-adrenoceptors (α1AR- and ß2AR) were found at a prevalence of 50%. Elimination of agAABs by immunoadsorption (IA) was successfully applied in cardiovascular disease. The IMAD trial (Efficacy of immunoadsorption for treatment of persons with Alzheimer dementia and agonistic autoantibodies against alpha1A-adrenoceptor) investigates whether the removal of α1AR-AABs by a 5-day IA procedure has a positive effect (improvement or non-deterioration) on changes of hemodynamic, cognitive, vascular and metabolic parameters in patients with suspected Alzheimer’s clinical syndrome within a one-year follow-up period. Methods: the IMAD trial is designed as an exploratory monocentric interventional trial corresponding to a proof-of-concept phase-IIa study. If cognition capacity of eligible patients scores 19–26 in the Mini Mental State Examination (MMSE), patients are tested for the presence of agAABs by an enzyme-linked immunosorbent assay (ELISA)-based method, followed by a bioassay-based confirmation test, further screening and treatment with IA and intravenous immunoglobulin G (IgG) replacement. We aim to include 15 patients with IA/IgG and to complete follow-up data from at least 12 patients. The primary outcome parameter of the study is uncorrected mean cerebral perfusion measured in mL/min/100 gr of brain tissue determined by magnetic resonance imaging with arterial spin labeling after 12 months. Conclusion: IMAD is an important pilot study that will analyze whether the removal of α1AR-agAABs by immunoadsorption in α1AR-agAAB-positive patients with suspected Alzheimer’s clinical syndrome may slow the progression of dementia and/or may improve vascular functional parameters. MDPI 2020-06-19 /pmc/articles/PMC7356934/ /pubmed/32575439 http://dx.doi.org/10.3390/jcm9061919 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Stracke, Sylvia Lange, Sandra Bornmann, Sarah Kock, Holger Schulze, Lara Klinger-König, Johanna Böhm, Susanne Vogelgesang, Antje von Podewils, Felix Föel, Agnes Gross, Stefan Wenzel, Katrin Wallukat, Gerd Prüss, Harald Dressel, Alexander Kunze, Rudolf Grabe, Hans J. Langner, Sönke Dörr, Marcus Immunoadsorption for Treatment of Patients with Suspected Alzheimer Dementia and Agonistic Autoantibodies against Alpha1a-Adrenoceptor—Rationale and Design of the IMAD Pilot Study |
title | Immunoadsorption for Treatment of Patients with Suspected Alzheimer Dementia and Agonistic Autoantibodies against Alpha1a-Adrenoceptor—Rationale and Design of the IMAD Pilot Study |
title_full | Immunoadsorption for Treatment of Patients with Suspected Alzheimer Dementia and Agonistic Autoantibodies against Alpha1a-Adrenoceptor—Rationale and Design of the IMAD Pilot Study |
title_fullStr | Immunoadsorption for Treatment of Patients with Suspected Alzheimer Dementia and Agonistic Autoantibodies against Alpha1a-Adrenoceptor—Rationale and Design of the IMAD Pilot Study |
title_full_unstemmed | Immunoadsorption for Treatment of Patients with Suspected Alzheimer Dementia and Agonistic Autoantibodies against Alpha1a-Adrenoceptor—Rationale and Design of the IMAD Pilot Study |
title_short | Immunoadsorption for Treatment of Patients with Suspected Alzheimer Dementia and Agonistic Autoantibodies against Alpha1a-Adrenoceptor—Rationale and Design of the IMAD Pilot Study |
title_sort | immunoadsorption for treatment of patients with suspected alzheimer dementia and agonistic autoantibodies against alpha1a-adrenoceptor—rationale and design of the imad pilot study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356934/ https://www.ncbi.nlm.nih.gov/pubmed/32575439 http://dx.doi.org/10.3390/jcm9061919 |
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