Perispinal etanercept for neuroinflammatory disorders.
Excess TNF is centrally involved in the pathogenesis of a variety of neuroinflammatory disorders, including Alzheimer's disease, other forms of dementia, intervertebral disc-related pain, and related disorders. TNF causes neuronal dysfunction, regulates synaptic mechanisms, and mediates amyloid-induced disruption of molecular mechanisms involved in memory. Perispinal administration of etanercept, a potent anti-TNF fusion protein, is a treatment modality whose rapid clinical effects may be related to modulation of these TNF-related mechanisms, particularly the role of TNF as a gliotransmitter capable of regulating synaptic transmission. This approach utilizes therapeutic delivery of etanercept across the dura via the cerebrospinal venous system, a confluence of the venous plexuses of the spine and the brain, in which flow is bi-directional owing to the absence of venous valves.
Tobinick
Edward
E
Institute for Neurological Research, a private medical group, inc. 100 UCLA Medical Plaza, Suites 205-210, Los Angeles, CA 90095, United States. etmd@ucla.edu
D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003704:Dementia / Q000188:drug therapy / Q000503:physiopathology; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007278:Injections, Spinal; D009437:Neuralgia / Q000188:drug therapy / Q000503:physiopathology; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D009435:Synaptic Transmission / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept