alt="Blogging on Peer-Reviewed Research"
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, href="http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a602013.html"
rel="tag">etanercept ( href="http://enbrel.com/" rel="tag">Enbrel®)
has been shown, in at least one case, to result in significant
cognitive improvement in a patient with href="http://www.ninds.nih.gov/disorders/alzheimersdisease/alzheimersdisease.htm"
rel="tag">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 href="http://www.sciencedaily.com/releases/2008/01/080109091102.htm">Science
Daily and href="http://www.medpagetoday.com/Neurology/AlzheimersDisease/tb1/7938">Medical
News Today. Bloggers have written about
it, too ( href="http://marydpinkowish.typepad.com/healthsifter/2008/01/did-they-revers.html">1
Here the abstract for the article:
cognitive improvement in Alzheimer’s disease following perispinal
Edward L. Tobinick and Hyman Gross
Journal of Neuroinflammation 2008, 5:2
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
href="http://www.mocatest.org/">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
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 href="http://www.videolan.org/vlc/">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:
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
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
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
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.