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...
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2020-06-01
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author | Sylvia Stracke Sandra Lange Sarah Bornmann Holger Kock Lara Schulze Johanna Klinger-König Susanne Böhm Antje Vogelgesang Felix von Podewils Agnes Föel Stefan Gross Katrin Wenzel Gerd Wallukat Harald Prüss Alexander Dressel Rudolf Kunze Hans J. Grabe Sönke Langner Marcus Dörr |
author_facet | Sylvia Stracke Sandra Lange Sarah Bornmann Holger Kock Lara Schulze Johanna Klinger-König Susanne Böhm Antje Vogelgesang Felix von Podewils Agnes Föel Stefan Gross Katrin Wenzel Gerd Wallukat Harald Prüss Alexander Dressel Rudolf Kunze Hans J. Grabe Sönke Langner Marcus Dörr |
author_sort | Sylvia Stracke |
collection | DOAJ |
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. |
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spelling | doaj.art-9aaeaa8831dd47729d9036e9ad1c9db62023-11-20T04:21:29ZengMDPI AGJournal of Clinical Medicine2077-03832020-06-0196191910.3390/jcm9061919Immunoadsorption for Treatment of Patients with Suspected Alzheimer Dementia and Agonistic Autoantibodies against Alpha1a-Adrenoceptor—Rationale and Design of the IMAD Pilot StudySylvia Stracke0Sandra Lange1Sarah Bornmann2Holger Kock3Lara Schulze4Johanna Klinger-König5Susanne Böhm6Antje Vogelgesang7Felix von Podewils8Agnes Föel9Stefan Gross10Katrin Wenzel11Gerd Wallukat12Harald Prüss13Alexander Dressel14Rudolf Kunze15Hans J. Grabe16Sönke Langner17Marcus Dörr18Department for Internal Medicine A, Nephrology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, GermanyInstitute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Neurology, University Medicine Greifswald, 17475 Greifswald, GermanyStrategic Research Management, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, GermanyCoordinating Centre for Clinical Trials, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Neurology, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Neurology, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Neurology, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Internal Medicine B, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, GermanyBerlin Cures GmbH, 13125 Berlin, GermanyBerlin Cures GmbH, 13125 Berlin, GermanyGerman Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, GermanyDepartment of Neurology, Carl-Thiem-Klinikum, 03048 Cottbus, GermanyScience Office, Hessenhagen 2, 17268 Flieth-Stegelitz, GermanyDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, GermanyInstitute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Internal Medicine B, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, GermanyBackground: 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.https://www.mdpi.com/2077-0383/9/6/1919Alzheimer’s clinical syndromedementiaimmunoadsorptionautoantibodiesα1-Adrenergic receptor |
spellingShingle | Sylvia Stracke Sandra Lange Sarah Bornmann Holger Kock Lara Schulze Johanna Klinger-König Susanne Böhm Antje Vogelgesang Felix von Podewils Agnes Föel Stefan Gross Katrin Wenzel Gerd Wallukat Harald Prüss Alexander Dressel Rudolf Kunze Hans J. Grabe Sönke Langner Marcus Dörr Immunoadsorption for Treatment of Patients with Suspected Alzheimer Dementia and Agonistic Autoantibodies against Alpha1a-Adrenoceptor—Rationale and Design of the IMAD Pilot Study Journal of Clinical Medicine Alzheimer’s clinical syndrome dementia immunoadsorption autoantibodies α1-Adrenergic receptor |
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 | Alzheimer’s clinical syndrome dementia immunoadsorption autoantibodies α1-Adrenergic receptor |
url | https://www.mdpi.com/2077-0383/9/6/1919 |
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