Etanercept

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"Give with a free hand, but give only your own."
-- J.R.R. Tolkien The Children of Hurin
- Etanercept -

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Observations:

Drug 'can reverse Alzheimer's symptoms in minutes' The Evening Standard (UK)

"A drug used for arthritis can reverse the symptoms of Alzheimer's "in minutes". It appears to tackle one of the main features of the disease - inflammation in the brain."

Lead author of the study Edward Tobinick, of the University of California and Director of the Institute for Neurological Research

Published in the Journal of Neuroinflammation, 5.2 (Jan 9, 2008): p2

http://www.enbrel.com/
http://en.wikipedia.org/wiki/Etanercept

Reversal Of Alzheimer's Symptoms Within Minutes In Human Study
ScienceDaily (Jan. 9, 2008)
An extraordinary new scientific study, which for the first time documents marked improvement in Alzheimer’s disease within minutes of administration of a therapeutic molecule, has just been published in the Journal of Neuroinflammation. This new study highlights the importance of certain soluble proteins, called cytokines, in Alzheimer’s disease. The study focuses on one of these cytokines, tumor necrosis factor-alpha(TNF), a critical component of the brain’s immune system. Normally, TNF finely regulates the transmission of neural impulses in the brain. The authors hypothesized that elevated levels of TNF in Alzheimer’s disease interfere with this regulation. To reduce elevated TNF, the authors gave patients an injection of an anti-TNF therapeutic called etanercept. Excess TNF-alpha has been documented in the cerebrospinal fluid of patients with Alzheimer’s. The new study documents a dramatic and unprecedented therapeutic effect in an Alzheimer’s patient: improvement within minutes following delivery of perispinal etanercept, which is etanercept given by injection in the spine. Etanercept (trade name Enbrel) binds and inactivates excess TNF. Etanercept is FDA approved to treat a number of immune-mediated disorders and is used off label in the study...
http://www.sciencedaily.com/releases/2008/01/080109091102.htm

Arthritis drugs could help prevent memory loss after surgery, study suggests
Imperial College London
News and Events
November 1, 2010

Anti-inflammatory drugs currently used to treat diseases such as rheumatoid arthritis may also help prevent cognitive problems after surgery, according to a new study by researchers at Imperial College London and University of California, San Francisco (UCSF).

The research also reveals for the first time that a specific inflammatory response in the brain may explain why many patients experience memory loss or other forms of cognitive dysfunction after surgery or critical illness... Previous studies have linked post-operative cognitive decline with the rise in blood levels of a cytokine called interleukin-1 beta (IL-1β), which is involved in inflammation. For this study, Maze and his colleagues studied another cytokine called tumour necrosis factor (TNF-α), which is known to regulate the immune system's inflammatory response before interleukin-1 is produced...
http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_2-11-2010-9-27-7

Anti-TNF Therapies for Rheumatoid Arthritis Could Reduce Alzheimer’s Risk
American College of Rheumatology (ACR)
11/1/2010 8:00 AM EDT

Newswise - Anti-TNF therapies commonly used to treat rheumatoid arthritis have been found to potentially reduce the risk of developing Alzheimer's dementia among people with rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Atlanta...
http://www.newswise.com/articles/view/570196/?sc=rsmn

TNF-alpha modulation for treatment of Alzheimer's disease: a 6-month pilot study

Abstract

Context
Current pharmacologic treatments for Alzheimer's disease (AD) do not prevent long-term clinical deterioration. Tumor necrosis factor (TNF)-alpha, a proinflammatory cytokine, has been implicated in the pathogenesis of AD.

Objective
To investigate the use of a biologic TNF-alpha inhibitor, etanercept was given by perispinal extrathecal administration for the treatment of AD.

Methods
This was a prospective, single-center, open-label, pilot (proof-of-concept) study, in which 15 patients with mild-to-severe AD were treated for 6 months. We administered etanercept, 25-50 mg, once weekly by perispinal administration. Main outcome measures included the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), and the Severe Impairment Battery (SIB).

Results
The average age of our patient population was 76.7. The mean baseline MMSE was 18.2 (n = 15); the mean baseline ADAS-Cog was 20.8 (n = 11); and the mean baseline SIB was 62.5 (n = 5). There was significant improvement with treatment, as measured by all of the primary efficacy variables, through 6 months: MMSE increased by 2.13 ± 2.23, ADAS-Cog improved (decreased) by 5.48 ± 5.08, and SIB increased by 16.6 ± 14.52.

Conclusion
An increasing amount of basic science and clinical evidence implicates inflammatory processes and resulting glial activation in the pathogenesis of AD. This small, open-label pilot study suggests that inhibition of the inflammatory cytokine TNF-alpha may hold promise as a potential approach to AD treatment. Further study in randomized, placebo-controlled clinical trials is merited.
http://www.ncbi.nlm.nih.gov/pubmed/16926764
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1785182/

Arthritis Drugs Linked to Lower Odds of Alzheimer's
TNF Blockers Associated With 55% Reduced Risk of Dementia
By Charlene Laino
WebMD Health News

Nov. 9, 2010 (Atlanta) -- People who take drugs called TNF blockers for rheumatoid arthritis may potentially reduce their odds of developing Alzheimer's disease, preliminary research suggests.

The use of TNF blockers was associated with a 55% lower risk of Alzheimer's disease in people with rheumatoid arthritis... TNF blockers neutralize a protein, called tumor necrosis factor alpha (TNF), that is overproduced in inflammatory diseases like rheumatoid arthritis [...and chronic infections like H.pylori, etc. -ed].

"Studies have shown that TNF is also elevated in the cerebrospinal fluid of Alzheimer's patients and that higher levels correlate with the progression of the disease," Chou tells WebMD.

To further explore the possible association between rheumatoid arthritis, Alzheimer's, and TNF blockers, Chou and colleagues combed through a medical and pharmacy claims database that included information on 8.5 million U.S. adults.

Chou presented his findings here at the annual meeting of the American College of Rheumatology... When they further analyzed the risk according to the three TNF blockers studied, the researchers found that Enbrel was associated with a nearly 70% reduced risk of Alzheimer's... "Theoretically, it may cross the blood-brain earlier more easily,"...
http://www.webmd.com/alzheimers/news/20101108/arthritis-drugs-linked-lower-odds-alzheimers?src=RSS_PUBLIC

Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration.
J Neuroinflammation. 2008 Jan 9;5:2.
http://www.ncbi.nlm.nih.gov/pubmed/18184433

TNF-alpha modulation for treatment of Alzheimer's disease: a 6-month pilot study.
MedGenMed. 2006 Apr 26;8(2):25.
http://www.ncbi.nlm.nih.gov/pubmed/16926764

Regulation of peripheral inflammation by spinal p38 MAP kinase in rats.
PLoS Med. 2006 Sep;3(9):e338.
http://www.ncbi.nlm.nih.gov/pubmed/16953659

Intrathecal inflammation precedes development of Alzheimer's disease.
http://www.ncbi.nlm.nih.gov/pubmed/12933918

Anti-TNF therapy in the injured spinal cord.
Esposito E, Cuzzocrea S.
Trends Pharmacol Sci. 2011 Feb;32(2):107-15.
At the time of approval of etanercept by the FDA, the role of TNF in neurological disorders was incompletely understood. Novel methods of drug delivery were needed because of the high molecular weight of etanercept and the problems faced by large molecules in traversing the blood–brain barrier(BBB). Perispinal methods were designed for selective delivery of etanercept. Perispinal administration results in rapid local delivery of etanercept to the vertebral venous system and the cerebrospinalfluid(CSF), with rapid local delivery to sites of TNF excess[52]. Rapid response suggests immediate neutralization of excess TNF, resulting in normalization of synaptic mechanisms.
PubMed 21185611
http://www.ncbi.nlm.nih.gov/pubmed/21185611

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