Oral treatment with the all-d-peptide RD2 enhances cognition in aged beagle dogs - A model of sporadic Alzheimer's disease

Janine Kutzsche; Sarah Schemmert; Tuyen Bujnicki; Christian Zafiu; Steffen Halbgebauer; Victoria Kraemer-Schulien; Marlene Pils; Lara Blömeke; Julia Post; Andreas Kulawik; Dagmar Jürgens; Wolfgang M Rossberg; Michael Hümpel; Oliver Bannach; Markus Otto; Joseph A Araujo; Antje Willuweit; Dieter Willbold

doi:10.1016/j.heliyon.2023.e18443

Oral treatment with the all-d-peptide RD2 enhances cognition in aged beagle dogs - A model of sporadic Alzheimer's disease

Heliyon. 2023 Jul 29;9(8):e18443. doi: 10.1016/j.heliyon.2023.e18443. eCollection 2023 Aug.

Authors

Janine Kutzsche¹, Sarah Schemmert¹, Tuyen Bujnicki¹, Christian Zafiu¹, Steffen Halbgebauer², Victoria Kraemer-Schulien¹, Marlene Pils^{1

3}, Lara Blömeke^{1

4}, Julia Post^{1

4}, Andreas Kulawik¹, Dagmar Jürgens¹, Wolfgang M Rossberg⁵, Michael Hümpel⁶, Oliver Bannach^{1

4

3}, Markus Otto², Joseph A Araujo⁷, Antje Willuweit⁸, Dieter Willbold^{1

4}

Affiliations

¹ Institute of Biological Information Processing, Structural Biochemistry (IBI-7), Forschungszentrum Jülich, Jülich, Germany.
² Institute of Experimental Neurology, Ulm University Hospital, Ulm, Germany.
³ attyloid GmbH, Düsseldorf, Germany.
⁴ Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
⁵ ConsultWMR, Potsdam, Germany.
⁶ KAIROSmetics UG, Berlin, Germany.
⁷ InterVivo Solutions, Fergus, Canada.
⁸ Institute of Neuroscience and Medicine, Medical Imaging Physics (INM-4), Forschungszentrum Jülich, Jülich, Germany.

Abstract

Disease-modifying therapies to treat Alzheimer's disease (AD) are of fundamental interest for aging humans, societies, and health care systems. Predictable disease progression in transgenic AD models favors preclinical studies employing a preventive study design with an early pre-symptomatic treatment start, instead of assessing a truly curative approach with treatment starting after diagnosed disease onset. The aim of this study was to investigate the pharmacokinetic profile and efficacy of RD2 to enhance short-term memory and cognition in cognitively impaired aged Beagle dogs - a non-transgenic model of truly sporadic AD. RD2 has previously demonstrated pharmacodynamic efficacy in three different transgenic AD mouse models in three different laboratories. Here, we demonstrate that oral treatment with RD2 significantly reduced cognitive deficits in cognitively impaired aged Beagle dogs even beyond the treatment end, which suggests in combination with the treatment dependent CSF tau oligomer decrease a disease-modifying effect of RD2 treatment.

Keywords: Alzheimer's disease; Aβ oligomers; Cognitively impaired aged Beagle dogs; Disease-modifying therapy; Pharmacodynamics; Pharmacokinetics; Sporadic AD animal model; Tau oligomers.