11 January 2008

Enbrel: Etanercept -- A New Conceptual Approach for Treating Alzheimer's and Other Diseases

Enbrel (Etanercept) is a Tumour Necrosis Factor (TNF) blocker originally developed to treat arthritis (RA and JRA). Its use has been enlarged to treat psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis. Even more astounding, Etanercept has shown efficacy in treating forms of diabetes, advanced heart failure, and most recently, Alzheimer's Disease.
Of particular relevance to intersections between neuroinflammation and neurodegeneration is the ability of TNF to increase expression of interleukin-1 (IL-1), which in turn increases production of the precursors necessary for formation of amyloid plaques, neurofibrillary tangles, and Lewy bodies. More recent data have revealed that TNF, one of the few gliotransmitters, has strikingly acute effects on synaptic physiology. These complex influences on neural health suggest that manipulation of this cytokine might have important impacts on diseases characterized by glial activation, cytokine-mediated neuroinflammation, and synaptic dysfunction. Toward such manipulation in Alzheimer's disease, a six-month study was conducted with 15 probable-Alzheimer patients who were treated weekly with perispinal injection of Etanercept, an FDA-approved TNF inhibitor that is now widely used for treatment of rheumatoid arthritis and other systemic diseases associated with inflammation. The results demonstrated that perispinal administration of etanercept could provide sustained improvement in cognitive function for Alzheimer patients. Additionally, the authors were impressed by the striking rapidity with which these improvements occurred in the study patients.

How rapid were these improvements? Would you believe, for some patients, "in minutes?"
The drug, called Enbrel, is injected into the spine where it blocks a chemical responsible for damaging the brain and other organs.

A pilot study carried out by U.S. researchers found one patient had his symptoms reversed "in minutes".

Other patients have shown some improvements in symptoms such as forgetfulness and confusion after weekly injections over six months.

The study of 15 patients with moderate to severe Alzheimer's has just been published in the Journal of Neuroinflammation by online publishers Biomed Central.

... Sue Griffin, a researcher at the University of Arkansas for Medical Sciences, said: 'It is unprecedented to see cognitive and behavioural improvement in a patient with established dementia within minutes of therapeutic intervention.

'This gives all of us in Alzheimer research a tremendous new clue about new avenues of research.' Enbrel is not approved for treating Alzheimer's in the U.S. or the UK and is regarded as highly experimental, said Dr Griffin.

There is also evidence that Etanercept can normalize mitochondrial function in some conditions. Clearly, TNF-mediated inflammation plays a significant role in a very broad array of disease processes.

While the vast majority of such research findings take place in the western world, the benefits from their discovery will quickly disseminate to the far corners of the entire world. This is one dimension of the "seed effect" of a freer intellectual environment within the west. What a shame to ever lose that.

To watch a fascinating animation of TNF and Etanercept at work, go here.

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