Abstract
Background: Increasing basic science and clinical evidence implicates inflammatory processes and resulting glial activation in the pathogenesis of Alzheimers Disease. Excess TNF-alpha, a cytokine with pleotropic effects in the CNS, has been suggested to be involved in the pathogenesis of AD. In addition to its pro-inflammatory effects, TNF-alpha affects synaptic transmission; and glutamate, NMDA, and amyloid pathways. More specifically, TNF-alpha, produced by glia, has been shown to affect both synaptic strength and to mediate synaptic scaling, a homeostatic mechanism important to the control of neural networks. A recently published small, open-label pilot study suggested that inhibition of the inflammatory cytokine TNF-alpha utilizing the perispinal administration of etanercept may lead to sustained cognitive improvement for six months in patients with mild, moderate, and severe Alzheimer ’ s disease. Results: Continued open-label clinical experience with this new treatment modality, now for more than two years, suggests that weekly maintenance treatment with perispinal etanercept may have a sustained positive effect. In addition, rapid clinical improvement, within minutes of dosing, has been observed on a repeated basis in multiple patients. Discussion: It is hypothesized that perispinal administration of etanercept may enable rapid delivery to the CNS via the cerebrospinal venous system, resulting in improvement in synaptic mechanisms which have been dysregulated by excess TNF-alpha. TNF-alpha modulation in Alzheimers disease may also act by influencing glutamate, NMDA, amyloid and other inflammatory pathways. Methods of perispinal administration, as described in the pilot study, may prove useful for delivering other therapeutics, particularly large molecules, to the CNS. Further study in randomized, placebo-controlled clinical trials and in basic science studies is merited.
Keywords: TNF, etanercept, Alzheimer's, synaptic scaling, dementia, cytokines
Current Alzheimer Research
Title: Perispinal Etanercept for Treatment of Alzheimers Disease
Volume: 4 Issue: 5
Author(s): Edward Tobinick
Affiliation:
Keywords: TNF, etanercept, Alzheimer's, synaptic scaling, dementia, cytokines
Abstract: Background: Increasing basic science and clinical evidence implicates inflammatory processes and resulting glial activation in the pathogenesis of Alzheimers Disease. Excess TNF-alpha, a cytokine with pleotropic effects in the CNS, has been suggested to be involved in the pathogenesis of AD. In addition to its pro-inflammatory effects, TNF-alpha affects synaptic transmission; and glutamate, NMDA, and amyloid pathways. More specifically, TNF-alpha, produced by glia, has been shown to affect both synaptic strength and to mediate synaptic scaling, a homeostatic mechanism important to the control of neural networks. A recently published small, open-label pilot study suggested that inhibition of the inflammatory cytokine TNF-alpha utilizing the perispinal administration of etanercept may lead to sustained cognitive improvement for six months in patients with mild, moderate, and severe Alzheimer ’ s disease. Results: Continued open-label clinical experience with this new treatment modality, now for more than two years, suggests that weekly maintenance treatment with perispinal etanercept may have a sustained positive effect. In addition, rapid clinical improvement, within minutes of dosing, has been observed on a repeated basis in multiple patients. Discussion: It is hypothesized that perispinal administration of etanercept may enable rapid delivery to the CNS via the cerebrospinal venous system, resulting in improvement in synaptic mechanisms which have been dysregulated by excess TNF-alpha. TNF-alpha modulation in Alzheimers disease may also act by influencing glutamate, NMDA, amyloid and other inflammatory pathways. Methods of perispinal administration, as described in the pilot study, may prove useful for delivering other therapeutics, particularly large molecules, to the CNS. Further study in randomized, placebo-controlled clinical trials and in basic science studies is merited.
Export Options
About this article
Cite this article as:
Tobinick Edward, Perispinal Etanercept for Treatment of Alzheimers Disease, Current Alzheimer Research 2007; 4 (5) . https://dx.doi.org/10.2174/156720507783018217
DOI https://dx.doi.org/10.2174/156720507783018217 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Protein Nano-Fibrilar Structure and Associated Diseases
Current Proteomics Implications of Prion Protein Biology
Current Neurovascular Research Palmitoylethanolamide Regulates Production of Pro-Angiogenic Mediators in a Model of β Amyloid-Induced Astrogliosis <i>In Vitro</i>
CNS & Neurological Disorders - Drug Targets Metabotropic Glutamate Receptors as Therapeutic Targets for Cognitive Disorders
Current Topics in Medicinal Chemistry Other Drugs Acting on Nervous System Associated with QT-Interval Prolongation
Current Drug Safety Default Mode Network Connectivity and Related White Matter Disruption in Type 2 Diabetes Mellitus Patients Concurrent with Amnestic Mild Cognitive Impairment
Current Alzheimer Research Alpha7 Neuronal Nicotinic Receptor: A Pluripotent Target for Diseases of the Central Nervous System
CNS & Neurological Disorders - Drug Targets Mitochondria-Mediated Oxidative Stress: Old Target for New Drugs
Current Medicinal Chemistry Off-Label Trazodone Prescription: Evidence, Benefits and Risks
Current Pharmaceutical Design Hyperhomocysteinemia, Pteridines and Oxidative Stress
Current Drug Metabolism Epigenetic Drugs for Multiple Sclerosis
Current Neuropharmacology Serotonin and Human Cognitive Performance
Current Pharmaceutical Design COVID-19-associated Coagulopathy and Thromboembolism: Determination of Their Patterns and Risk Factors as Predictors of Mortality Among Severe COVID-19 Patients
Current Vascular Pharmacology The Role of Adipocytokines and Neurohormonal Dysregulation in Metabolic Syndrome
Current Diabetes Reviews Reviewing the Cardiovascular Complications of HIV Infection After the Introduction of Highly Active Antiretroviral Therapy
Current Drug Targets - Cardiovascular & Hematological Disorders The Role of the ATP-Binding Cassette Transporter P-Glycoprotein in the Transport of β-Amyloid Across the Blood-Brain Barrier
Current Pharmaceutical Design Sepsis in the Central Nervous System and Antioxidant Strategies with Nacetylcysteine, Vitamins and Statins
Current Neurovascular Research The Importance of Citicoline in Combined Treatment in Dementia: What did the Citimem Study Teach us?
Reviews on Recent Clinical Trials Role of Wnt Signaling in the Control of Adult Hippocampal Functioning in Health and Disease: Therapeutic Implications
Current Neuropharmacology The Role of MAPK's Signaling in Mediating ApoE4-Driven Pathology In Vivo
Current Alzheimer Research