The Corpus Callosum

href="http://www.researchblogging.org/"> alt="Blogging on Peer-Reviewed Research"
src="http://www.researchblogging.org/public/citation_icons/rb2_large_gray.png"
height="50" width="80">
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, 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
href="http://nattomatto.blogspot.com/2008/01/drug-found-to-reverse-alzheimers.html">2
href="http://writenow.wordpress.com/2008/01/11/promise-of-a-cure-for-alzheimers/">3
href="http://sayanythingblog.com/entry/a_drug_that_can_reverse_the_effects_of_alzheimers_in_minutes/">4
5).

Here the abstract for the article:

href="http://www.jneuroinflammation.com/content/5/1/2/abstract">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)


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 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
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 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:

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.  

Comments

  1. #1 qetzal
    January 14, 2008

    I agree, there’s ample reasons for skepticism here. That would be so even if the authors weren’t promoting this as their patented off-label use. Since they are, I think the potential for bias is enormous. The authors want it to work because they want to make money off it (and no doubt want to help patients also). The families want it to work to help their sick relatives. Everybody involved is highly disposed to see improvement, and I’m guessing there’s plenty of room for subjectivity in the MOCA.

    It wouldn’t be necessary for Amgen to sponsor a formal development program on this. An Alzheimer’s research center could easily do a proper double blind placebo controlled study to see if this is real. It wouldn’t be any more bureaucratically cumbersome or expensive than lots of other physician-initiated studies on approved drugs.

    The patent angle is interesting. It is certainly possible to gain a patent on a novel use for an existing drug. It’s also true that MD’s can normally prescribe any approved drug for any condition they think medically appropriate, even if it’s a new use that’s not covered in the drug’s package insert.

    I’m not sure how that gets resolved, but I think the INR may have another problem. They’re (apparently) promoting this off-label use of Enbrel. That may be illegal. It would be illegal if Amgen did it, anyway.

  2. #2 Sandra Porter
    January 14, 2008

    There have been studies where anti-inflammatory drugs – like ibuprofen – slowed or seemed to protect against Alzheimer’s disease. It’s possible that if the tissue damage and memory loss comes from macrophages attacking cells with ß-amyloid deposits, then maybe Enbrel might be protective.

    If the results of this study can be repeated, this is pretty good news!

  3. #3 Hank Roberts
    February 22, 2008

    I’ve also seen hints that inflammation is involved in the cognitive decline that hits some older people after anesthesia.

    http://dx.doi.org/10.1016/S0889-8537(05)70149-8

    I know that concern puts some people off routine screening like colonoscopy that requires anestheia.

The site is undergoing maintenance presently. Commenting has been disabled. Please check back later!