recombinant human erythropoietin / Max Planck Institute, Pfizer - LARVOL DELTA

Forebrain-specific loss of erythropoietin provokes compensatory upregulation of different EPO receptors. (PubMed, Mol Psychiatry) - "Using the previously published single-nuclei-RNA-seq dataset, we further confirm the suggested compensatory mechanism, wherein EPO loss or reduction drives elevated EPOR expression, adding another layer to the intricate regulation of EPO signaling in hippocampal pyramidal neurons. Collectively, these data may explain the lack of behavioral and negative cognitive consequences upon forebrain-wide EPO elimination."

Journal • EMX1 • EPHB4

Transcriptional dynamics of the oligodendrocyte lineage and its regulation by the brain erythropoietin system. (PubMed, Nat Commun) - "Mice lacking EPOR from mature oligodendrocytes show subtle deficiencies of adult myelination in hippocampal fimbria and mild working memory deficits. These gain- and loss-of-function experiments may further suggest EPO as clinically safe treatment for remyelination therapies."

Journal • Solid Tumor • EPO

Multiple Mammalian Cytokines and Erythropoietin-Mimetic Peptides Protect Insect Neurons via Phylogenetically Conserved Cytokine Receptor-Like Factor 3 (CRLF3). (PubMed, J Neurochem) - "In contrast to vertebrate classical Epo receptor, which is only activated by Epo and EMP1, CRLF3 has an extended and more generalist ligand spectrum to mediate neuroprotection. This wide ligand spectrum may support the hypothesis of CRLF3 being the evolutionary precursor of various vertebrate-specific cytokine receptors and may qualify this more general cell protective receptor as a target for pharmacological intervention in neurodegenerative processes."

Journal • CNS Disorders

Innovative Strategies towards Precision Medicine in Treatment Resistant Schizophrenia and severe psychotic disorder (WFSBP 2025) - "This symposium will also address innovative therapeutic strategies, including the role of the cerebral erythropoietin (EPO) system in enhancing cognitive function in schizophrenia. Understanding the interplay between immune pathways, synaptic dysfunction, and treatment response could pave the way for targeted interventions, improving early identification and management of TRS. By integrating cutting-edge findings from proteomics, immunology, and novel treatment strategies, this session will contribute to the development of precision medicine approaches in psychotic disorders."

CNS Disorders • Psychiatry • Schizophrenia • B2M • IL12A • IL17A

Knock Out of miRNA-30a-5p and Reconstitution of the Actin Network Dynamics Partly Restores the Impaired Terminal Erythroid Differentiation during Blood Pharming. (PubMed, Stem Cell Rev Rep) - "Previously, we developed imBMEP-A, the first erythroid cell line derived from reticulocyte progenitors, which maintains robust hemoglobin expression and erythroid differentiation in the presence of erythropoietin (EPO) despite its immortalized state...These interventions improved viability, restored actin network formation, and increased terminal erythropoiesis, yielding 22.1 ± 1.7% more orthochromatic erythroblasts. These findings establish a foundation for optimizing imBMEP-A cells for therapeutic use and advancing the understanding the pathophysiology of erythroleukemia."

Journal • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • MIR30A • MYC

Tolerability and first hints for potential efficacy of motor-cognitive training under inspiratory hypoxia in health and neuropsychiatric disorders: A translational viewpoint. (PubMed, Neuroprotection) - "Erythropoietin in serum increases under hypoxia and flow cytometry analysis of blood reveals several immune cell types to be mildly modulated by hypoxia. To obtain reliable information regarding the "add-on" value of inspiratory on top of functional hypoxia, induced by motor-cognitive training, a single-blind study-with versus without inspiratory hypoxia-is essential and outlined here."

Journal • Autism Spectrum Disorder • CNS Disorders • Depression • Genetic Disorders • Mental Retardation • Psychiatry

Forebrain specific loss of erythropoietin provokes a compensatory upregulation of different EPO receptors (Neuroscience 2024) - "Using our single-nuclei-RNA-seq dataset, we identify forebrain expression of Emx mainly in excitatory neurons with no alterations upon EPO. Collectively, these data explain the lack of behavioral and cognitive consequences on forebrain-wide elimination of EPO."

CNS Disorders • EMX1 • EPHB4

Erythropoietin restrains the inhibitory potential of interneurons in the mouse hippocampus. (PubMed, Mol Psychiatry) - "Metabolism and inhibitory potential of interneuron subgroups are compromised, leading to greater excitability of pyramidal neurons. To conclude, improvement by rhEPO of neuropsychiatric phenotypes may partly owe to restrictive control over interneurons, facilitating re-connectivity and synapse development."

Journal • Preclinical • Alzheimer's Disease • Autism Spectrum Disorder • CNS Disorders • Cognitive Disorders • Genetic Disorders • Mental Retardation • Psychiatry • Schizophrenia

Effects of erythropoietin on cognitive impairment and prefrontal cortex activity across affective disorders: A randomized, double-blinded, placebo-controlled trial. (PubMed, J Psychopharmacol) - P2 | "Nevertheless, the findings support the validity of dPFC target engagement as a biomarker model for pro-cognitive effects, according to which treatments that do not improve cognition should not modulate dPFC activity. EudraCT no.: 2016-004023-24; ClinicalTrials.gov identifier: NCT03315897."

Clinical • Journal • Alzheimer's Disease • Bipolar Disorder • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Neuroprotective Effects of Moderate Hypoxia: A Systematic Review. (PubMed, Brain Sci) - "We identified 58 eligible studies (k = 8 human studies with N = 274 individuals; k = 48 animal studies) reporting the effects of hypoxia on cognition, motor function, neuroimaging, neuronal/synaptic morphology, inflammation, oxidative stress, erythropoietin, neurotrophins, and Alzheimer's disease markers...Low-dose intermittent or continuous hypoxia repeated for 30-240 min sessions, preferably in combination with motor-cognitive training, produced beneficial effects, and high-dose hypoxia with longer (≥6 h) durations and chronic exposure produced more adverse effects. Larger and methodologically stronger translational studies are warranted."

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation

Effect of erythropoietin on cognitive side-effects of electroconvulsive therapy in depression: A randomized, double-blind, placebo-controlled trial. (PubMed, Eur Neuropsychopharmacol) - P2 | "The absence of global cognition changes with ECT and EPO, coupled with the specific impact of EPO on autobiographical memory recall speed and memory-related parietal cortex activity, suggests that assessing autobiographical memory may provide increased sensitivity in evaluating and potentially preventing cognitive side-effects of ECT. TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT03339596, EudraCT no.: 2016-002326-36."

Adverse events • Clinical • Journal • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

Intravenous erythropoietin improves cognitive performance in patients with schizophrenia (ECNP 2023) - "Overall, our findings support previous reports demonstrating ameliorated cognitive performance resulting from treatment with EPO. Importantly, EPO does not counter the impact of psychopathological phenomena inherent in schizophrenia which is reflected by our findings in P3. Nonetheless, EPO constitutes a promising approach to mitigate cognitive deficits in several patient groups allowing to improve functional outcome."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

Exploiting moderate hypoxia to benefit patients with brain disease: Molecular mechanisms and translational research in progress. (PubMed, Neuroprotection) - "Hypoxia-induced erythropoietin expression in the brain likely plays a decisive role in these processes, which can be imitated by recombinant human erythropoietin treatment...It thereby provides the ground for exploiting moderate inspiratory plus functional hypoxia to treat individuals with brain disease. Finally, it sketches a planned multistep pilot study in healthy volunteers and first patients, about to start, aiming at improved performance upon motor-cognitive training under inspiratory hypoxia."

Journal • CNS Disorders • EPO

Erythropoietin re-wires cognition-associated transcriptional networks. (PubMed, Nat Commun) - "Using a Cre-based approach to visually distinguish pre-existing from newly formed pyramidal neurons for patch-clamp recordings, we learn that rhEPO treatment differentially affects excitatory and inhibitory inputs. Our findings provide mechanistic insight into how EPO modulates neuronal functions and networks."

Journal • Hematological Disorders

Pro-cognitive effects of intravenous erythropoietin in patients with schizophrenia (SIRS 2023) - "Keyword Keywords Cognitive Decline in Schizophrenia Pharmacological Treatment neurodevelopmental disorders psychosis, cognition, negative symptoms, neurobiology Poster Award Yes Poster Award Eligibility - Young Investigator Yes Poster Award Eligibility - SIRS Membership No Please list all co-authors for this poster submission. * Presenting Author First Name Last Name Affiliation Mishal * Qubad * Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University 2Karlotta Jacobs Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University Catherine Barnes-Scheufler Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University Mareike Aichholzer Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University Hannah Wendy Department of Psychiatry, Psychosomatic..."

Clinical • CNS Disorders • Schizophrenia

For decades against the mainstream - From erythropoietin and hypoxia as novel treatment strategies to deep phenotyping in neuropsychiatric disorders. (PubMed, Psychiatry Res) - No abstract available

Journal • CNS Disorders • Mental Retardation • Psychiatry

Introducing the brain erythropoietin circle to explain adaptive brain hardware upgrade and improved performance. (PubMed, Mol Psychiatry) - "Here we delineate the brain EPO circle as working model explaining adaptive 'brain hardware upgrade' and improved performance. In this fundamental regulatory circle, neuronal networks, challenged by motor-cognitive tasks, drift into transient 'functional hypoxia', thereby triggering neuronal EPO/EPOR expression."

Journal • Review • CNS Disorders • Mental Retardation • Psychiatry • Solid Tumor

Addressing the 'hypoxia paradox' in severe COVID-19: literature review and report of four cases treated with erythropoietin analogues. (PubMed, Mol Med) - "Substitution of EPO may-among other beneficial EPO effects in severe COVID-19-circumvent downstream consequences of the 'hypoxia paradox'. A double-blind, placebo-controlled, randomized clinical trial for proof-of-concept is warranted."

Clinical • Journal • Review • Critical care • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Psychiatry • Respiratory Diseases

Brain erythropoietin fine-tunes a counterbalance between neurodifferentiation and microglia in the adult hippocampus. (PubMed, Cell Rep) - "Surprisingly, EPO affects microglia in phases, initially by inducing apoptosis, later by reducing proliferation, and overall dampens microglia activity and metabolism, as verified by selective genetic targeting of either the microglial or pyramidal neuronal EPO receptor. We suggest that during accelerating neuronal differentiation, EPO acts as regulator of the CSF1R-dependent microglia."

Clinical • Journal • CSF1R

Effect of Early Recombinant Human Erythropoietin on Neurodevelopmental Outcomes at Age 5 Years. (PubMed, JAMA) - No abstract available

Journal

CaMKIIα Expressing Neurons to Report Activity-Related Endogenous Hypoxia upon Motor-Cognitive Challenge. (PubMed, Int J Mol Sci) - "We previously introduced the brain erythropoietin (EPO) circle as a model to explain the adaptive 'brain hardware upgrade' and enhanced performance...To conclude, task-associated activity triggers neuronal functional hypoxia as a local and brain-wide reaction mediating adaptive neuroplasticity. Hypoxia-induced genes such as EPO drive neuronal differentiation, brain maturation, and improved performance."

Journal • HIF1A • SESN2

Thrombocytopenia in Patients with Chronic Hepatitis C Virus Infection. (PubMed) - Mediterr J Hematol Infect Dis - "Thrombopoietin-mimetic agents, in particular, eltrombopag and romiplostim, have been shown to be safe and effective for HCV-related thrombocytopenia in various studies, and they increase platelet count without eliciting any immunogenicity Other treatment modalities including newer TPO analogues-AMG-51, PEG-TPOmp and AKR-501, recombinant human IL-11 (rhIL-11, Oprelvekin), recombinant human erythropoietin (rhEPO), danazol and L-carnitine have shown promising early result with improving thrombocytopenia. Thrombocytopenia in chronic HCV infection remain a major problem, however the recent change in DAAs without IFN, as the frontline therapy for HCV, permit to avoid the dilemmas associated with initiating or maintaining IFN based anti-viral therapy."

Journal • Review • Biosimilar • Hepatitis C Virus • Immunology • Venous Thromboembolism

Erythropoietin improves hypoxic-ischemic encephalopathy in Neonatal Rats after Short-term Anoxia by Enhancing Angiogenesis. (PubMed) - Brain Res - "While this up-regulation, and changes in the histopathologic and functional outcomes were abolished by SU5416. Our data indicate that rhEPO can enhance angiogenesis, reduce white matter damage, and promote cognitive recovery through VEGF/VEGFR2 signaling pathway in anoxia rats."

Journal • Biosimilar • Gene Therapies • Oncology • Reperfusion Injury • Sarcoma

Four-Week Studies of Oral Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of Anemia. (PubMed) - "GSK1278863 was generally safe and well tolerated at the doses and duration studied. GSK1278863 may prove an effective alternative for managing anemia of CKD."

Journal • Biosimilar

Recombinant human erythropoietin improves functional recovery in patients with severe traumatic brain injury: A randomized, double blind and controlled clinical trial. (PubMed) - Clin Neurol Neurosurg - "Treatment with five doses of recombinant human erythropoietin is associated with an improved functional recovery in patients with severe traumatic brain injury. This treatment does not seem to increase the risk of thromboembolic events or severe infections."

Journal • Biosimilar • Immunology