The Corpus Callosum

Sounds too good to be true.  Perhaps it is.  For one, there is only one published case.  For another, it has to be injected near the spine in order to have this effect.  The arthritis medication, etanercept (Enbrel^®) has been shown, in at least one case, to result in significant cognitive improvement in a patient with Alzheimer's Disease within minutes of administration.  The effect lasts for days.

The case report was published in the Journal of Neuroinflammation, at the open-access publisher, BioMed Central.  It also has been reported at Science Daily and Medical News Today.  Bloggers have written about it, too (1 2 3 4 5).

Here the abstract for the article:

Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration
Edward L. Tobinick and Hyman Gross
Journal of Neuroinflammation 2008, 5:2
doi:10.1186/1742-2094-5-2

Abstract (provisional)

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Substantial basic science and clinical evidence suggests that excess tumor necrosis factor-alpha (TNF-alpha) is centrally involved in the pathogenesis of Alzheimer's disease. In addition to its pro-inflammatory 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 efficacy of etanercept, a biologic antagonist of TNF-alpha, delivered by perispinal administration, for treatment of Alzheimer's disease over a period of six months has been previously reported in a pilot study. This report details rapid cognitive improvement, beginning within minutes, using this same anti-TNF treatment modality, in a patient with late-onset Alzheimer's disease. Rapid cognitive improvement following perispinal etanercept may be related to amelioration of the effects of excess TNF-alpha on synaptic mechanisms in Alzheimer's disease and provides a promising area for additional investigation and therapeutic intervention.

Some key points to the article:

The authors have treated several patients; many have improved.  The original protocol called for monthly cognitive testing.  Such testing could not detect rapid improvement.   The person they report upon in the article was tested separately from the main protocol.

The patient was a retired physician, 81 years old.  He generally was healthy except for the dementia.  He was taking atorvastatin, low dose aspirin, and galantamine 8mg per day.  His mental status examination, one day prior to treatment, "revealed a dignified appearing man who appeared younger than his stated age, neatly groomed and socially outgoing in a superficial engaging fashion."   This one patient may not be representative of the general dementia patient population.

The patient ended up receiving five injections (one per week).  Treaters, raters, and the patient all were aware of the treatment being given.

Prior to treatment, the patient's score on the Montreal Cognitive Assessment test (MOCA) was 7 out of 30 possible (indicating moderate-to-severe dementia). Two hours after the first injection, his MOCA score was 15.  Two weeks after the last injection, his MOCA score was 14.

The article provides a decent review of the drug, etanercept, its mechanism of action, and the physiology of the drug's main target, TNF-alpha.  However, the authors can't really say how the drug works.  Most of the research done on the drug relates to its anti-inflammatory effect in rheumatoid arthritis.  While informative, that does not tell us how the drug affects Altzheimer's Disease.  

The article has obvious limitations.  It reports on only one case.  It was not double blind.  The protocol used was not a formal research protocol.  

Of interest to some, perhaps, is the fact that the authors include a link to a short movie.  It shows an interview with some family members, as they talk about how amazed they were at the effect of the treatment.  [Note: the movie wouldn't play for me until I downloaded it and started it with the VLC Media Player (which plays almost everything).]

Now for a little background.  The treatment is administered at the Institute for Neurological Research (INR), which is a private medical group.  They have patented the treatment.  Here is a snippet from their website:

The INR anti-TNF program* is a unique, pioneering, patented** off-label treatment program for selected patients with Alzheimer's Disease who have failed to adequately respond to conventional medical treatment.

I must say this: My first reaction to this is to be both amazed and hopeful.  My second reaction is to be somewhat skeptical and a little bit perturbed.  The case report is straightforward enough.  The video, however, could just as well be taken from some nutty altie treatment (not all alternative treatments are nutty, but some are) or from a faith-healing session.  It is not presented as an advertisement, but it is likely to have the same effect.  

Note that I am explicitly not comparing the treatment to faith healing.  I am saying that the video serves no scientific purpose, but it does have an emotionally compelling quality.  I find that distasteful.

The INR is providing this treatment to the public.  It is not FDA approved.  Given the level of desperation that Alzheimer's families feel, and the invasiveness and cost of the treatment, I would prefer that they follow a more conventional path for the research and development of this treatment.  

Granted, if the pharmaceutical company that makes Enbrel (Amgen) were to undertake a traditional drug development process, it would take a long time, would be bureaucratically cumbersome, and would be enormously expensive.  But doing it in accordance with FDA approval guidelines would provide a framework for oversight.  The system is not perfect -- far from it -- but it exists for a reason.

As a side note, I'll also mention that I am skeptical of the concept of a patent for this type of thing.  The drug is already available, FDA approved for rheumatoid arthritis and similar conditions.  Traditionally, once a drug is approved for one purpose, physicians are free to use it for other purposes (as long as they exercise good medical judgment and practice).  The issuance of a patent, in this context, would seem to contradict a longstanding tradition in medicine.