Immunoadsorption for treatment of patients with suspected alzheimer dementia and agonistic autoantibodies against alpha1a-adrenoceptor —rationale and design of the imad pilot study

Abstract

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.