Has anyone seen this? http://www.sciencedaily.com/releases/2008/01/080109091102.htm
The first paragraph from the article: "ScienceDaily (Jan. 9, 2008) — An extraordinary new scientific study, which for the first time documents marked improvement in Alzheimer’s disease within minutes of administration of a therapeutic molecule(Enbrel), has just been published in the Journal of Neuroinflammation."

I used to take Enbrel for my rheumatoid arthritis, I was surprised to see it as a possible treatment for Alz. I'm optimistic about it's apparent effectiveness in the trial. Anyone out there (or loved one) take part in the study?

My grandmother died of Alz and my aunt is in the advanced stages of the disease, I'd love to get her into an Enbrel trial.

(my first post - hope it's in the right place )

I came back to the board here after a long absence to make sure this information was available. It sounds extremely positive. I think I will begin searching for doctors who will consider this treatment for my mother.

Keep us posted.

I know some of the Brenham doctors.

eoadcaregiver@yahoo.com

BTW, at the International Alzheimer’s and Dementia Conference (ICAD) conference in Philadelphia about 3 1/2 years ago, I saw a presentation about brain cells going dormant for a very long time before dying. Though not mentioned, that would account for parts of the brain to suddenly start working – a characteristic of Alzheimer’s when someone who has not been talking, says something in context. It would also allow for immediate dramatic improvement in symptoms.

Here's a paste-link to the article on Bloomburg.com (a business website) - it has a few more details.

http://www.bloomberg.com/apps/news?pid=20601202&sid=a0j.t_nzzQcQ&refer=healthcare#

I was wondering if the 15 study participants were still receiving Enbrel. From the article, it looks like a least one has continued treatment.

"``This absolutely has the potential to be a disease-modifying treatment,'' said Edward Tobinick, one of the study's authors and an associate professor at the UCLA School of Medicine. ``Since this report, our patient has received several other doses, and he's continued to show a therapeutic benefit.''"

Are there any Enbrel clinical trials in the UK?
What are the expected timescales for results?

I heard about this Enbrel study on ABC news last night. Apparently, an 81 yr old was injected in the spine with Enbrel. Within 10 minutes he had his memory restored. I would also like to know if any Doctors in Orange County are prescribing this treatment or if there are any clinical trials in this location.

I called the Institute for Neurological Research, 310-824-6199. This is a private practice for Dr. Tobinick. There are no clinical trials available, but you can receive treatment if accepted after a $300 first appointment and then a $650 Medical evaluation appointment. If accepted, the weekly treatments cost $600 plus the drug which cost approximately $220 per week. I do not think any insurance company will pay for treatments since it is considered experimental. So, why aren't there any trials if this is such a wonder drug for alz.??????

I'm sure a larger, double-blind study is in the works - possibly several.
This FDA webpage shows the new drug development process: http://www.fda.gov/cder/handbook/develop.htm

In the Bloomberg article the representative from Amgen/Wyeth said, "The concept is interesting,'' said Michael Lampe, a spokesman for Madison, New Jersey-based Wyeth, in a telephone interview today. ``In general, we don't discuss early stage research."

I'm betting the other TNF-a drug manufacturers are going to be on this one quick, hence the hush-hush reply. (The other TNF-a inhibitors are Humira from Abbott and Remicade from Centocor)

I read this from the Journal of Neuroinflammation 2008:
Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept (etanercept = Enbrel) administration


Published: 9 January 2008

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

http://www.jneuroinflammation.com/content/5/1/2

I googled "Institute for Neurological Research" and found Dr. Tobinick's website.
http://www.nrimed.com/index.html

They also have a patient handbook of sorts (a PDF file) http://www.nrimed.com/INR.AD8.pdf

It's says they have video testimonials from patient's family members. I couldn't watch, it's too much for me.

I'm of two minds on this now. On one hand this is exactly what I hoped for - that this treatment would become available immediately - on the other hand, now that Dr T has "set up shop" as it were, replete with a patent and emotional video 'testimonials', I'm increasingly skeptical. Darn.

Well, we'll see what our local doctors think of this . . .

I watched the videos and am impressed.

I would be skeptical except that the national news has been on this discovery too.

I hope trials will begin soon.

Why aren't the other members of this "trial" mentioned? Is it because they contracted meningitis or encepholitis and died? I hate to be a spoiler here but something is just not quite right.

Technically it wasn't a clinical trial - something like this is usually called a 'case report'.

In other news articles they do mention similar results in the other 14 patients. (Basically they say, "all 15 showed marked and sustained improvement".)

No one died - yet, this hasn't been tested and no one knows what problems, side effects etc, may show up.

I was so excited when I first heard about Enbrel, but I am getting increasingly suspicious as I google Dr. Tobinek. I think he is an internal medical doctor and a dermatologist. I can not find him on any list of UCLA doctors in the neurology department - maybe I need to check dermatologist!!! Again, if this is so promising, I would think there would be a legitamate clinical trial.

I think it's Dr. Edward Tobinick, and while he is an assistant professor of clinical medicine at UCLA (the university), it's a research/teaching position - he isn't a doctor at UCLA medical center.

As a physician he has his own practice, called the Institute for Neurological Research.

I read his bio on his website - his medical degree is from UC of San Diego. His post-grad residency was at UCLA Medical Center.

I'm really interested in what our local doctors will think of all of this!

Much as I hate to rain on the parade ... everything I can find indicates this is not the cure-all the news media have suggested. (For the record, the news media is probably the last place I'd go for reliable information on new medicines.)

If I understand the exceptionally vague reports by Dr Tobinick correctly, his treatment requires an injection into the spinal column in the neck once a week, EVERY week, FOREVER. One of the other people posting to this discussion found out this treatment costs $820 per treatment, i.e., $42,640 per year.

I suspect that receiving injections into the spinal column in the neck is a relatively risky procedure done even once, let alone once a week.

While much fuss is made about his most recent publication (of two), and while he claims to have been administering this treatment to patients for three years, Tobinick cites only a *single* case.

Similarly, he discussed only a single case in the earlier (2006) report. He also glossed over the fact that one of the fifteen patients in that study died, and there was no autopsy to confirm cause of death.

There were no control patients, so it is impossible to tell if there really was any significant improvement in comparison with, e.g., a placebo.

Plus, while I'm no statistician, the numbers he cites do not appear to be statistically significant improvement over baseline, anyway. In my book, a change of 2.13 -/+ 2.23 points is not significant.

Finally, it should be noted that any improvement that *is* noted does not change with additional injections. The MMSE pops up (purportedly) by 2 points and just stays there, flat-line, for the six months of the study. (Also, the graphs in the report do *not* match the numbers in the abstract.) This just does not make sense to me, unless the "improvement" is an artifact.

There was absolutely no follow-up on any patients from the 2006 study, which lasted six months. So there is no way of knowing what happened to the patients after treatment was discontinued. Also, there's no way of knowing what happens if treatment *is* continued (see below.)

Moreover, the drug he is using has many potential serious side effects, even without the risky perispinal administration technique. According to MedicineNet.com, "Since etanercept has been on the market, there have been reports of multiple sclerosis, myelitis, optic neuritis in patients using the drug. Etanercept is not recommended for persons with preexisting disease of the central nervous system (brain and/or spinal cord) or for those with multiple sclerosis, myelitis, or optic neuritis. Additionally, rare cases of seriously low blood counts (pancytopenia) have been reported in patients using etanercept. Since etanercept is a relatively new drug, there is limited information on long-term risks."

Wikipedia notes, "After a number of studies and reports of adverse reactions in patients receiving anti-TNF alpha therapy (including serious and sometimes fatal blood disorders, infections, rare reports of lymphoma and solid tissue cancers, rare reports of serious liver injury, and rare reports of demyelinating central nervous system disorders), rare reports of congestive heart failure, the U.S. Food and Drug Administration issued a warning to doctors appearing in the respective product labeling of these drugs instructing them to screen and monitor potential patients more carefully."

Note that these side effects have been observed with standard injection techniques, *not* injection into the spinal cord.

Dr Tobinick has not received any funding to support his "research." The patients have paid for the treatments. This also makes me extremely skeptical.

That said, perhaps there actually is some, temporary, benefit of the injections (provided one survives.) Many serious researchers, using carefully designed experiments with suitable controls, are studying the role of TNF-alpha in diseases such as Alzheimer's. However, those who are exploring the development of new drugs are looking at small-molecule inhibitors, which will cross the blood-membrane barrier and therefore can be taken orally and do not have to be injected into the spine. More importantly, they are looking for drugs that will prevent the formation of TNF-alpha, which intuitively appears to be a much better approach than trying to inhibit TNF-alpha after it has been formed. See, for example, Tweedie D, Sambamurti K, Greig NH; 2007; TNF-alpha inhibition as a treatment strategy for neurodegenerative disorders: new drug candidates and targets; Curr Alzheimer Res 4(4):378-85.

So ... I'll be tracking research on TNF-alpha synthesis inhibitors, and see how that goes. But I won't be rushing my husband up to Dr Tobinick's clinic any time soon.

The Alzheimer's Association has it's official take on the whole Enbrel matter posted under the NEWS/EVENTS section on the AA homepage.

I too am hopeful/skeptical of the use of Enbrel for Alzheimer's. My father is in stage 5 and has been involved in past clinical trials and therefore is not a candidate for future trials. I have had a consult with the INR and will patiently await any new information as it becomes available. I was directed to read an article available on www.medscape.com.(free service)
Read Anti-TNF-Alpha Therapy Produces Rapid Improvement in Alzheimer's Disease. This article gives a little more info. The one patient that improved immediately following Enbrel injection was able to correctly name 9/10 objects and before treatment could name 1/10. The article also states that Dr. Tobinick would like to "partner with academic institutions to help design clinical trials." As it states in the article this is not a cure for AD. But it may give us some hope into improving the quality of life for those with AD. I was also directed to read "Current Alzheimer's Research" Dec. 2007.

For ~$1770 I'm amazed that someone in the Los Angeles area hasn't given it a shot yet (sorry). Seems straightforward enough, if it works in 10 minutes then this is incredible, if not then it's not that much money.

Continued treatment also isn't that much. From what I understand weekly treatment is only at the beginning and then it becomes monthly.

I think it is very important to read the following very thorough analysis from Jan. 21, 2008, and ALL of the ensuing comments, both pro and con:
http://www.alzforum.org/new/detail.asp?id=1738
Gabrielle Strobel has pointed out some issues that may have been overlooked in the rush to view intraspinal Enbrel as an instant cure.

I really can't understand how this Doctor is giving treatments, and charging enormous fees, if this treatment is still being studied and researched. Can anyone enlighten me?

Read the Alzforum's detailed investigation of Dr. Tobinick and his study:
http://www.alzforum.org/new/detail.asp?id=1738

"Scientists in the field were intrigued about the approach of inhibiting certain cytokines to treat inflammation in AD, yet also expressed reservations about the way these studies were conducted."

I called a local Rhumatologist and was told she gives Enbrel injections. hhhmm just wondering if the injection is the same Dr. Tobinik offers. I also was elated when I first heard of him but after being told the cost, I wonder why it's not shared with all the Neuroligists in the US. I was so encourged, then abruptly deflated.

I have had all the same questions go through my mind as all of you had, yet I am still hopeful. I am fortunate to live in the Los Angeles area so I called Dr. Tobinick's office 2 weeks ago and scheduled the appt for my Mom. I agree with one post, the amount to "find out" is very much worth it. I don't know if we can afford the weekly injections, but if I see great results, how could I stop? Our appt is tomorrow Jan 31, in which I believe they are going to do their initial assessment. I will report everything I find out. In the meantime, I took Mom to her regular Neurologist to ask what she thought about the new findings. Surprisingly, she was very hopeful and optimistic, speculating that they may approve this treatment before the end of this year, if all goes well. She was also concerned with encephalitis since that happened with a different drug a few years ago, which was injected directly into the brain or skull. I didn't tell her about my plans...I think I was afraid she'd tell me not to do it, and to just wait for the approval. Mom has declined a lot in the last 4 months, and I just don't want to wait. She's not having a good life as it is...

Felicia