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Drug Discov Today. 2009 Feb;14(3-4):168-77. doi: 10.1016/j.drudis.2008.10.005. Epub 2008 Dec 6.

Perispinal etanercept for neuroinflammatory disorders.

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  • 1Institute for Neurological Research, a private medical group, inc. 100 UCLA Medical Plaza, Suites 205-210, Los Angeles, CA 90095, United States.


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.

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