ArticleAlzheimer's & dementia (New York, N. Y.)2019
Hematologic safety of chronic brain-penetrating erythropoietin dosing in APP/PS1 mice.
Article in Alzheimer's & dementia (New York, N. Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Brain Delivery of Antibody-Derived Biologicals for Alzheimer's Disease: An Updated Narrative Review.Antibodies (Basel, Switzerland) · 2026Review
- Longitudinal pharmacokinetic and safety studies of an antibody-erythropoietin fusion protein for Alzheimer's disease.International journal of pharmaceutics: X · 2025Article
- Elucidating the Pivotal Neuroprotective Mechanisms and Therapeutic Variants of Erythropoietin in Neonatal Brain Injury.Current topics in medicinal chemistry · 2025Review
- Phase-targeted erythropoietin derivatives for traumatic brain injury: bridging mechanisms to precision therapy.Frontiers in neurology · 2025Review
- The Effects of a Blood-Brain Barrier Penetrating Erythropoietin in a Mouse Model of Tauopathy.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Efficacy and Safety of a Brain-Penetrant Biologic TNF-α Inhibitor in Aged APP/PS1 Mice.Pharmaceutics · 2022Article
- IgG Fusion Proteins for Brain Delivery of Biologics via Blood-Brain Barrier Receptor-Mediated Transport.Pharmaceutics · 2022Review
- A Historical Review of Brain Drug Delivery.Pharmaceutics · 2022Review
- Full- versus Sub-Regional Quantification of Amyloid-Beta Load on Mouse Brain Sections.Journal of visualized experiments : JoVE · 2022Article
- Recombinant human erythropoietin ameliorates cognitive dysfunction of APP/PS1 mice by attenuating neuron apoptosis via HSP90β.Signal transduction and targeted therapy · 2022Article
- Unravelling the potential neuroprotective facets of erythropoietin for the treatment of Alzheimer's disease.Metabolic brain disease · 2022Review
- Biologic TNF-α inhibitors reduce microgliosis, neuronal loss, and tau phosphorylation in a transgenic mouse model of tauopathy.Journal of neuroinflammation · 2021Article
- Targeting the transferrin receptor to develop erythropoietin for Alzheimer's disease.Neural regeneration research · 2020Article
- Acute and Chronic Dosing of a High-Affinity Rat/Mouse Chimeric Transferrin Receptor Antibody in Mice.Pharmaceutics · 2020Article
- Eliminating Fc N-Linked Glycosylation and Its Impact on Dosing Consideration for a Transferrin Receptor Antibody-Erythropoietin Fusion Protein in Mice.Molecular pharmaceutics · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
introductionLow blood-brain barrier (BBB) penetration and hematopoietic side effects limit the therapeutic development of erythropoietin (EPO) for Alzheimer's disease (AD). A fusion protein of EPO and a chimeric monoclonal antibody targeting the mouse transferrin receptor (cTfRMAb) has been engineered. The latter drives EPO into the brain via receptor-mediated transcytosis across the BBB and increases its peripheral clearance to reduce hematopoietic side effects of EPO. Our previous work shows the protective effects of this BBB-penetrating EPO in AD mice but hematologic effects have not been studied. Herein, we investigate the hematologic safety and therapeutic effects of chronic cTfRMAb-EPO dosing, in comparison to recombinant human EPO (rhu-EPO), in AD mice.
methodsMale APPswe PSEN1dE9 (APP/PS1) mice (9.5 months) were treated with saline (n = 11), and equimolar doses of cTfRMAb-EPO (3 mg/kg, n = 7), or rhu-EPO (0.6 mg/kg, n = 9) 2 days/week subcutaneously for 6 weeks, compared to saline-treated wild-type mice (n = 10). At 6 weeks, exploration and memory were assessed, and mice were sacrificed at 8 weeks. Spleens were weighed, and brains were evaluated for amyloid beta (Aβ) load and synaptophysin. Blood was collected at 4, 6 and 8 weeks for a complete blood count and white blood cells differential.
resultscTfRMAb-EPO transiently increased reticulocyte counts after 4 weeks, followed by normalization of reticulocytes at 6 and 8 weeks. rhu-EPO transiently increased red blood cell count, hemoglobin and hematocrit, and significantly decreased mean corpuscular volume and reticulocytes at 4 weeks, which remained low at 6 weeks. At 8 weeks, a significant decline in red blood cell indices was observed with rhu-EPO treatment. Exploration and cognitive deficits were significantly worse in APP/PS1-rhu-EPO mice. Both cTfRMAb-EPO and rhu-EPO decreased 6E10-positive brain Aβ load; however, cTfRMAb-EPO and not rhu-EPO selectively reduced brain Aβ DISCUSSION: Chronic treatment with cTfRMAb-EPO results in better hematologic safety, behavioral, and therapeutic indices compared with rhu-EPO, supporting the development of this BBB-penetrable EPO analog for AD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.