Tocilizumab’s effect on cognitive deficits induced by intracerebroventricular administration of streptozotocin in Alzheimer’s model

Elçioğlu, Hatice; Aslan, Ersin; Ahmad, Sarfraz; Alan, Saadet; Şalva, Emine; Elçioğlu, Ömer H.; Kabasakal, Levent

doi:10.1007/s11010-016-2762-6

Cited by 28 publications

(14 citation statements)

References 37 publications

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“…Efficacy of another TNF-α inhibitoretanercept has been studied in Alzheimer's disease (Tobinick, 2012); however, a recent placebocontrolled, double-blind, phase 2 trial of subcutaneous etanercept demonstrated no significant changes in cognition, behaviour and global functioning (Butchart et al, 2015). Preclinical evidence also indicates that toclizumab, which is a monoclonal antibody inhibiting IL-6 signalling, might improve spatial memory and learning in Alzheimer's disease animal model (Elcioglu et al, 2016).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Cytokine alterations and cognitive impairment in major depressive disorder: From putative mechanisms to novel treatment targets

Misiak

Beszłej

Kotowicz

et al. 2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Section: Accepted Manuscriptmentioning

confidence: 99%

Cytokine alterations and cognitive impairment in major depressive disorder: From putative mechanisms to novel treatment targets

Misiak

Beszłej

Kotowicz

et al. 2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…143 However, levels of inflammatory markers in COVID-19 patients may be lower than levels observed in secondary insults such as acute respiratory distress syndrome (ARDS) that could be associated with SARS-CoV-2 infection. 144 The interleukin (IL)-6 inhibitor, tocilizumab, reduces cognitive deficits in a mouse model of AD, 145 and IL-6 inhibitors are being studied in clinical trials for their efficacy in treating severe SARS-CoV-2 disease. 143 Long-term follow-up of these patients will enhance understanding of the role of IL-6 and SARS-CoV-2 in any subsequent neurodegeneration.…”

mentioning

confidence: 99%

Blood Biomarkers for Detection of Brain Injury in COVID-19 Patients

DeKosky

Kochanek

Valadka

et al. 2021

Journal of Neurotrauma

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus attacks multiple organs of coronavirus disease 2019 (COVID-19) patients, including the brain. There are worldwide descriptions of neurological deficits in COVID-19 patients. Central nervous system (CNS) symptoms can be present early in the course of the disease. As many as 55% of hospitalized COVID-19 patients have been reported to have neurological disturbances three months after infection by SARS-CoV-2. The mutability of the SARS-COV-2 virus and its potential to directly affect the CNS highlight the urgency of developing technology to diagnose, manage, and treat brain injury in COVID-19 patients. The pathobiology of CNS infection by SARS-CoV-2 and the associated neurological sequelae of this infection remain poorly understood. In this review, we outline the rationale for the use of blood biomarkers (BBs) for diagnosis of brain injury in COVID-19 patients, the research needed to incorporate their use into clinical practice, and the improvements in patient management and outcomes that can result. BBs of brain injury could potentially provide tools for detection of brain injury in COVID-19

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“…Animal data suggest that tocilizumab is safe and effective for treatment of severe acute pancreatitis and associated acute lung injury [22]. Further, tocilizumab had neuroprotective effects in a model of Alzheimer's disease [23].…”

Section: Background and Rationale {6a}mentioning

confidence: 99%

Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response after Out-of-Hospital Cardiac Arrest (IMICA): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial

Meyer

Wiberg

Grand

et al. 2020

Trials

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Background Resuscitated out-of-hospital cardiac arrest (OHCA) patients who remain comatose at admission are at high risk of morbidity and mortality. This has been attributed to the post-cardiac arrest syndrome (PCAS) which encompasses multiple interacting components, including systemic inflammation. Elevated levels of circulating interleukin-6 (IL-6), a pro-inflammatory cytokine, is associated with worse outcomes in OHCA patients, including higher vasopressor requirements and higher mortality rates. In this study, we aim to reduce systemic inflammation after OHCA by administering a single infusion of tocilizumab, an IL-6 receptor antibody approved for use for other indications. Methods Investigator-initiated, double-blinded, placebo-controlled, single-center, randomized clinical trial in comatose OHCA patients admitted to an intensive cardiac care unit. Brief inclusion criteria: OHCA of presumed cardiac cause, persistent unconsciousness, age ≥ 18 years. Intervention: 80 patients will be randomized in a 1:1 ratio to a single 1-h intravenous infusion of either tocilizumab or placebo (NaCl). During the study period, patients will receive standard of care, including sedation and targeted temperature management of 36 ° for at least 24 h, vasopressors and/or inotropes as/if needed, prophylactic antibiotics, and any additional treatment at the discretion of the treating physician. Blood samples are drawn for measurements of biomarkers included in the primary and secondary endpoints during the initial 72 h. Primary endpoint: reduction in C-reactive protein (CRP). Secondary endpoints (abbreviated): cytokine levels, markers of brain, cardiac, kidney and liver damage, hemodynamic and hemostatic function, adverse events, and follow-up assessment of cerebral function and mortality. Discussion We hypothesize that reducing the effect of circulating IL-6 by administering an IL-6 receptor antibody will mitigate the systemic inflammatory response and thereby modify the severity of PCAS, in turn leading to lessened vasopressor use, more normal hemodynamics, and better organ function. This will be assessed by primarily focusing on hemodynamics and biomarkers of organ damage during the initial 72 h. In addition, pro-inflammatory and anti-inflammatory cytokines will be measured to assess if cytokine patterns are modulated by IL-6 receptor blockage. Trial registration ClinicalTrials.gov Identifier: NCT03863015; submitted February 22, 2019, first posted March 5, 2019. EudraCT: 2018-002686-19; date study was authorized to proceed: November 7, 2018.

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Tocilizumab’s effect on cognitive deficits induced by intracerebroventricular administration of streptozotocin in Alzheimer’s model

Cited by 28 publications

References 37 publications

Cytokine alterations and cognitive impairment in major depressive disorder: From putative mechanisms to novel treatment targets

Cytokine alterations and cognitive impairment in major depressive disorder: From putative mechanisms to novel treatment targets

Blood Biomarkers for Detection of Brain Injury in COVID-19 Patients

Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response after Out-of-Hospital Cardiac Arrest (IMICA): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial

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