About the author

Dan Rhoads

Dan is a postdoc working at the University of Cyprus in developmental biology. He has a BSc in molecular biology and a PhD pharmacology and biochemistry.

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One of the more dreaded diseases that plague our elders is Alzheimer’s disease, which robs the afflicted of not just their memories, but their dignities as well. Research on the role of cytokines in disease progression has illuminated a therapy with great potential, according to a recent study.

Edward Tobinick and Hyman Gross, in a 2006 study¹, found that intraspinal injection of a potent anti-TNF therapeutic (etanercept) given to 15 patients rapidly and effectively relieved Alzheimer’s-related symptoms. The trouble with the original study, however, was that the IRB-approved clinical trial only included monthly testing, which was too long an interval, so they planned future studies. This time, Tobinick and Gross conducted a case study of an 81-y.o. man, exhibiting late-onset symptoms (Open Access, at the Journal of Neuroinflammation)². The results demonstrated a remarkable improvement in all areas of cognitive function related to Alzheimer’s symptoms within 2 hours, with improvement being sustained throughout the week until the patient’s return visit. Patients from the 2006 study still are better off than before their treatments at that time. It’s true, the placebo effect and variation from patient to patient cannot be ruled out, but the authors present several lines of evidence that treatment with TNF antagonists like etanercept really works:

1. The extreme rapidity of the effect
2. The extraordinary potency and selectivity of etanercept as an anti-TNF-alpha agent, due to its biologic nature and molecular structure
3. The various lines of scientific evidence which have suggested that synaptic dysfunction may be of key importance in the pathogenesis of Alzheimer’s disease
4. Evidence suggesting that TNF-alpha regulates synaptic transmission in the brain
5. Evidence suggesting that TNF-alpha mediates the synaptic dysfunction underlying cognitive and behavioral impairment produced by both beta-amyloid and beta-amyloid oligomers

Now, calling anti-TNF drugs a ‘cure’ may be jumping the gun – I don’t want to raise any false hopes – but you have to admit that this is a tremendous discovery. Further clinical studies will of course be needed though.

What is TNF anyway?

It’s full name is TNF-alpha, or tumor necrosis factor-alpha, and it belongs to a class of small proteins called cytokines. It regulates immune cells, and causes apoptotic cell death, cellular proliferation, differentiation, inflammation, tumorigenesis, and viral replication, for starters. As it promotes inflammation, ends up causing many of the clinical problems associated with autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, psoriasis and refractory asthma. In fact, etanercept is currently only approved by the FDA for treatment of rheumatoid arthritis.

In addition to its proinflammatory functions, TNF-alpha has recently been recognized to be a gliotransmitter that regulates synaptic function in neural networks. TNF-alpha has also recently been shown to mediate the disruption in synaptic memory mechanisms, which is caused by beta-amyloid and beta-amyloid oligomers. The ScienceDaily post also noted:

Similarly, the Neurotechnology Industry Organization has recently selected new treatment targets revealed by neuroimmunology (such as excess TNF) as one of the top 10 Neuroscience Trends of 2007. And the Dana Alliance for Brain Initiatives has chosen the pilot study using perispinal etanercept for Alzheimer’s for inclusion and discussion in their 2007 Progress Report on Brain Research.

1. Tobinick E, Gross H, Weinberger A, Cohen H. TNF-alpha modulation for treatment of Alzheimer’s disease: a 6-month pilot study. MedGenMed, 8(2):25 (2006). Pubmed
2. Tobinick E, Gross H. Rapid cognitive improvement in Alzheimer’s disease following perispinal etanercept administration. J Neuroinflammation, 5(1):2 (2008). DOI: 10.1186/1742-2094-5-2
3. Rosenberg PB. Clinical aspects of inflammation in Alzheimer’s disease. Int Rev Psychiatry, 17:503–514 (2005). Pubmed