Reversal Of Alzheimer's Symptoms Within Minutes In Human Study

[Duer 157099]

Source: Science Daily

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, has just been published in the Journal of Neuroinflammation.

(snip)

The new study documents a dramatic and unprecedented therapeutic effect in an Alzheimer’s patient: improvement within minutes following delivery of perispinal etanercept, which is etanercept given by injection in the spine. Etanercept (trade name Enbrel) binds and inactivates excess TNF. Etanercept is FDA approved to treat a number of immune-mediated disorders and is used off label in the study.

Read more: http://www.sciencedaily.com/releases/2008/01/080109091102.htm

---

I hope this is real! If so, very exciting!

[TwilightGardener]

1. I'm surprised that there's actually a "Journal of Neuroinflammation"--

Now THAT'S filling a niche!

[BOSSHOG]

4. That caught my eye as well

I need to consult with that publication after spending too much time with my brother in law.

[Recursion]

7. There's a journal for everything

Check out http://www.doaj.org/ for all the bizarre niche journals you could ever want...

[PATRICK]

11. I see those every day at work

Try working thousands of glossy copies of Gum Disease Journal sometime..or the skin disease pin-ups....ergh...

[MannyGoldstein]

23. Neuroinflammation is a *Big Deal*

It's turning out that most all bad diseases - dementia, and much or most cancer and much heart disease - have inflammation as a key link. Fish oil and statins, which are the two best things to take for improving life expectancy, work by reducing inflammation.

[kimmerspixelated]

29. Omega-3's purified fish oils

are the best, or alaskan salman..maybe a few others. It fights inflammation, and you are right, it appears to be the root of all diseases. Also at the root of most diseases is a vitamin or mineral deficiency. But I disagree about statins, especially not long-term.

[OKthatsIT]

40. Pure wild anchovy oils are even better.

But harder to find....Remember, the smaller the fish, on the food chain...less mercury.

[Barrett808]

41. Can we get the same benefit from non-fish oils?

'Cause I don't want to contribute to the accelerating destruction of the oceans...

[pink-o]

45. YES!!

...I'm a vegetarian, so I won't consume fish oils. In my 30 plus years on this diet, I've always found botanical substitutes for any animal remedy, and I did some research on Omega 3's.

The plant source? Walnuts.

You don't need many, just a few ounces a day. All nuts raise your HDL cholestrol and help your ratio to LDL, but walnuts have the exact properties as oily fish for Omegas.

Get nutty, Everyone!

[Duer 157099]

48. Ooooo! Thanks, I had no idea, and I love walnuts!

Not a vegetarian, but I loves me some nuts!

edit: and I'm so prone to suggestion, that I had to go grab some walnuts right now -- and since I had my postal scale sitting out, decided to weigh them. Did you know that about 5 whole walnuts is 1 OUNCE? So, 15 (30 halves) to get a few ounces. That seems like a lot of nuts to eat each day, no? Although I guess for vegetarians it's not huh?

Mmmmm, toasted walnuts, mmmmmmmm

[Barrett808]

53. Great, thanks!

:thumbsup:

[wolfgangmo]

59. There are better.

Try hemp oil. It beats walnuts hands down.

Of yah - if you read the article you will see that it just says that their drug worked and not that it worked well. As usual the follow up message is that it is very hopeful and will have great results with only a few years of full funding.

Sheesh.

[sofa king]

85. Gee, I think I'll try some hemp oil right now.

I can get the same benefits from inhaling it, right?

[JDPriestly]

87. The poster said hempoil, not hemp. Hrrmph!

[cyr330]

129. hehehe

I don't know, but I am certain it won't hurt to try!

[lildreamer316]

94. Welcome to DU! and thanks!

You just snswered the question I posted below. Thanks so much!
:hi:

[Lorien]

77. And flaxseed oil. n/t

[tridim]

97. And flax seeds and flaxseed meal.

I love flaxseed meal, it's great in almost everything. I also take the oil, it tastes/smells like the paint in those old paint by numbers kits.

[JDPriestly]

86. I eat walnuts every day. I just like them. I thought they were

a guilty pleasure. So your information makes me very happy. I just crave walnuts. It's very odd. Now I can enjoy them guilt-free. Thanks.

[earth mom]

92. How about peanuts or peanut butter? nt

[lildreamer316]

93. Umm...what if one is allergic to nuts?

Do I have to go back to fish oil?
Thanks for the info,btw, I will pass it on to the non-allergic.

[lynnertic]

98. Walnuts are also thought to

prevent hardening of the arteries

[JerseygirlCT]

100. Flax seed oil?

And doesn't have that fishy aftertaste, either.

[RoseMead]

115. Freeze the capsules to avoid the fishy taste

The doctor I worked for advised his patients to freeze their fish oil capsules before taking them. He said this allows the caps to be absorbed in the gut, elimintating the fishy taste or fishy burps. Patients that did this said it worked great. The cold doesn't harm the fish oil at all.

[JerseygirlCT]

116. That's an idea, thanks nt

[PADemD]

130. What about people who are allergic to walnuts?

[seasat]

134. Cool, I use walnut oil in my bread.

I never realized that it was a great source of Omega 3's. We only use bread from our bread machine and I liked the taste of walnut oil over the plain vegetable or canola oils.

[rainy]

46. the next best thing is oil from algae which is where the fish get their great

oils. They are harder to find, less potent, have to take more, but still a good alternative. Flax does not have all that fish oil has so it is not as good.

[Duer 157099]

125. Interesting re: omega-3 fa + uridine + choline @ MIT trial

http://web.mit.edu/newsoffice/2006/alzheimers.html

MIT brain researchers have developed a "cocktail" of dietary supplements, now in human clinical trials, that holds promise for the treatment of Alzheimer's disease.

For years, doctors have encouraged people to consume foods such as fish that are rich in omega-3 fatty acids because they appear to improve memory and other brain functions.

The MIT research suggests that a cocktail treatment of omega-3 fatty acids and two other compounds normally present in the blood, could delay the cognitive decline seen in Alzheimer's disease, which afflicts an estimated 4 million to 5 million Americans.

(snip)

The three compounds in the treatment cocktail -- omega-3 fatty acids, uridine and choline -- are all needed by brain neurons to make phospholipids, the primary component of cell membranes.

[OzarkDem]

132. Yes, a promising field in cancer research

great when these therapies may be able to work across the board in many diseases.

[greymattermom]

70. Hey

I'm sending them a paper next week. All about brain injury and aging. Important stuff.

[Duer 157099]

71. Cool - let us know if it gets accepted!

And since you're obviously in the field, what do you think of this study?

[greymattermom]

78. Inflammation

Makes the brain malfunction. The hippocampus and related structures are among the worst. The person who wrote about fish oil is correct.

[midnight]

81. Do you list any information on how to treat brain injury?

[greymattermom]

108. Working on it

We're doing studies on DHA depletion and supplementation, inflammation, blood brain barrier, aging. I'm known in the field, so to speak.

[BeyondThePale]

89. It is a relatively new journal and...

therefore does not have an impact factor reported by Thomson Scientific (they report an unofficial impact factor of 4.36, which is pretty good. Odd that such a striking finding was not submitted to a bigger impact journal, though...

[rfranklin]

122. Here's the link...

http://www.jneuroinflammation.com/

I cannot vouch for their accuracy.

[BOSSHOG]

2. That's great News

My Dad had Alzheimer's. That is one evil disease.

They used to call them insane asylums, now they are referred to as Alzheimers Wings at Nursing Homes.

[Missy M]

6. It sure is an evil disease.....

one I think we all fear. I hope there is something to that therapeutic molecule. Alzheimer's is devastating to both the victim and the victims family.

[intheflow]

8. Good news for my family, too.

My grandmother and aunt both had it. It's the one disease I really fear about growing old.

[BOSSHOG]

15. I think its justification

for assisted suicide. I'd hate for my wife to go through what my Step Mom did, even though it was for a relatively short time. The catch 22, one has to be of sound mind to make that decision but a living will should allow for it. The alternative is to be kept alive because of what "pro-lifers" believe while your families finances go down the sink. There was a man whose wife was in the nursing home my Dad was in. She had been in there for 13 years and was just a shell of a human being. The guy had nothing left. I don't consider that quality of life for anyone.

[intheflow]

25. I agree.

My cousins live in a 3-family townhouse they grew up in. When my grandmother got sick, she lived in one unit, my aunt lived in one unit with her younger children, and my eldest cousin in that family lived in the third unit. She helped her mother care for Gramma for five years, then less than five years after that she became primary care-giver to her mother, my aunt. My aunt lasted 10 years. My 35-year-old cousin had spent 2/3 of her life caring for loved ones who didn't recognize her and were physically and verbally abusive to her. Her first two marriages dissolved under the stress, and she could never get a job outside the home because she had was primary care-giver. To say my cousin was financially ruined would be a gross understatement. And of course she couldn't afford to put her mother in any kind of nursing facility; I think she only got some visiting nurse help the last year of her mother's life. Really hard to watch, even through my childhood, long-distance eyes.

[enough]

90. This is an accurate description of the devastation this disease can bring to families.

I had two elderly parents with dementia (one now deceased) and have spent some time on Alzheimer's forums on the net. The stories of family chaos and suffering from the disease are endless, and new ones keep coming every day.

[bigscott]

104. I agree with you Boss

My uncle recently passed after 2 years of this terrible disease. My mother has demanded I kill her before she gets to that point - of course I wont but you understand the desperation people feel when it comes to this terrible infliction.

[BOSSHOG]

111. I can easily

rationalize suicide in this case. I don't need religious mumbo jumbo. I would not want it to be anyone's decision but mine. My wife can grieve now and get on with her life or grieve in ten years after she has aged 30 years and lost all fiscal security.

I invite anyone who disagrees with me to have themselves locked in an Alzheimers ward for at least six months then come chat with me about the quality of life.

[emilyg]

57. Eventually caused my Dad's death.

[aquart]

3. Wow.

[Duer 157099]

5. Here's a link to a PDF of the actual article

http://www.jneuroinflammation.com/content/pdf/1742-2094-5-2.pdf

My mom is in the early stages -- I am going to see if I can get her into this trial.

I am sure I will get it too, so... planning ahead...

[roguevalley]

10. tremendous news

[Liberty Belle]

67. How? My Dad is in a nursing home with Alzheimer's; it is tearing us all up;

he sits and cries, wanting out...We are in San Diego. If you can tell me how to get him into this trial, I would give anything to get him included.

[Duer 157099]

73. I don't know yet, but it was done at UCLA, so not too far for you

I'm going to start making phone calls etc in the next few days and see what's what.

Also, since the drug is already available, all it really takes is an open-minded physician willing to try off label use. Try to send this study to your dad's physician and see what he thinks -- you just never know where it might lead.

[bdamomma]

9. That is good news, Alzheimers is a terrible disease, my mom suffered

from it.

[A-Long-Little-Doggie]

12. My mother-in-law is declining rapidly

This is good news...

[pattmarty]

13. I hope so too, but this drug is going to cost a GAZILLION dollars from the drug companies.

[tinrobot]

38. Enbrel is $713.92 per box, to be exact

http://www.drugstore.com/qxn58406042534_333181_sespider/enbrel/enbrel.htm

A box contains four vials... does that mean four doses or does one vial contain multiple doses? More importantly, I wonder how much an Alzheimers patient would need.

[Duer 157099]

39. Yikes, The dose is 25mg (1 vial) per week

so that's $700 per month... yikes... and being off-label, insurance wouldn't cover it.

Edit to remove disparaging remark about drug companies, since after all, they *did* develop the drug, so even at $700 per month, damn, it's better than no treatment. Damn the insurance companies if they don't cover it, that's what I really mean!

Plus, as a drug is used for more indications, the price should actually drop over time, especially if competition increases to develop other similar drugs

[lizerdbits]

42. When does the patent expire?

Generics will be much cheaper too.

[pattmarty]

91. Since the rule/law change, in the year 2214.

[pattmarty]

43. I am adding your edit back in; FUCK THE DRUG COMPANIES!

The drug companies work exactly the same way all the rest of the "supply & demand" BS does in the US. If someone needs the "product" let them pay what the "market" demands. So, if you need a drug, then you either pay or die/get sicker. I'll repeat louder this time in case no one heard the first time; FUCK THE DRUG COMPANIES! ! ! ! !

[TexasBushwhacker]

44. Not necessarily, re: insurance coverage

If they're already paying more for other medications, $700 may be cheap, and for the patient and their family, it's definitely cheaper than being disabled with Alzheimer's. Early onset Alzheimer's is defined as diagnosis before age 65 and only 10% of patients fall into that group, so this would primarily be a cost born by Medicare.

[pokercat999]

49. A good reason to nationalize the drug companies and

do the research in the NIH or public University Medical Centers withthe research being shared free worldwide.

[FiveGoodMen]

64. You got that right!

[The Wizard]

95. It's cheaper than a nursing home

We had to put my mom in one for dementia and she lasted about a year. Every time I'd go to visit I felt guilty for not being able to care for her at home. Every time I drive past the place I feel guilty, and it's on a main thoroughfare about two miles from home.
Inflammation is also thought to be the source of heart problems and fish oil and flax seed oil act as preventative remedies.

[daveskilt]

110. you may want to put the edit back in -

as I note in a post further down - this (like everything else in my field) is about money not patient care. this 'alternate use' for the drug is only coming to light now in order to extend the time amgen can charge full ticket price and not allow generics of this drug on the market.

[arendt]

14. I agree this is good news; but, for years, I have seen promising studies that didn't pan out...

The problem is, after decades and billions of dollars of research, the basic mechanism of AD is still up for debate - not to mention the unbelievably subtle effects that somehow kick off the cascade that get the AD mechanism up and running.

So, yay for these guys. But, it is ONE, ANECDOTAL study; not a valid, double blind study.

I know how awful this disease is. My wife is a psychologist, and she used to diagnose these people until she couldn't stand breaking people's hearts anymore. Maybe, when she can offer hope instead of a horrible, slow death, she will get back into the field.

In the meantime, at least some of our tax dollars are going for something helpful to humanity.

arendt

[Duer 157099]

18. I agree with your cautious response

but for people who are dealing with AD *now* and cannot wait for a cure or a thorough understanding of the mechanism, this might just be a good stop-gap measure to increase the quality of life for those with AD, understanding that it's not a cure.

I'm reading the article now, and it's convincing enough to make me want to look into it asap. Like most drugs/treatments, some people simply won't respond, for whatever reason, but when you have no other choice, there's not much to lose.

The nice thing is this drug is ALREADY on the market, so doing off-label testing is a very different matter than trying to get an experimental compound through the whole process.

Hell, 25mg of Enbrel and a 1cc syringe, some sterile water... a bit of knowledge of anatomy...

[Auntie Bush]

28. Now watch the price of Enbrel quadrupole to the tenth power!

This is such excellent news. I sure hope it's true.

I was my Mother's primary care giver for over 5 years. I felt like a prisoner myself as we couldn't go anywhere...plus all the nasty duties. I managed emotionally and physically until they told us we couldn't ever leave my Mother alone. I remember the Health aids were pretty pissed when I went over to the neighbors to ask a question and didn't get back for maybe 10 minutes. We had to hire someone to watch her ever time we wanted to go anywhere...and that's expensive and doesn't count as a medical expense. At that point I really resented being the care giver and wouldn't you know the other family members never offered to come here and give us a break. I'm sure that story resonates with many care givers. I'm wondering if I wouldn't take some sleeping pills if I ever got in that situation. However, when you get that serious you don't realize you are even sick!
This is one of the worst diseases on the planet earth! God help mankind
to find a cure. Let's hope he already has!

[Nothing Without Hope]

16. Thanks! ****The entire original article is FULL, OPEN ACCESS!!! ****

This journal seems to make one article per month open-access so everyone can read it without a subscription. It's another indication of the perceied importance of this report that it was chosen for open access. The pdf file of the article is here:

http://www.jneuroinflammation.com/content/pdf/1742-2094-5-2.pdf

Now that I've posted this I see that the link was also given earler in this thread, but given the importance, another mention of it isn't a bad idea.

[Duer 157099]

20. Not only that -- it was submitted on Nov 29th

and accepted *today* - and released for publication on the net the same day.

Now granted, this isn't Science, or Nature, or The Lancet, but sometimes papers are deliberately submitted to other journals simply to expedite the publication process (not always -- sometimes it's done because they know they have no chance of getting published in those other journals... and really, we don't know if this paper was submitted elsewhere several times before they decided to go here...)

[fed-up]

17. this part doesn't sound so good: "etanercept given by injection in the spine" nt

[Nothing Without Hope]

19. This is a way to get this preparation (an antibody) into the brain

by bypassing the blood-brain barrier. Future drug development could aim for a small molecule that could get through or some other approach. In the meantime, maybe they can come up with a slow-release pump (or gel or other approach) to deliver over a longer term.

[JerseygirlCT]

101. Probably sounds worse than it is

The idea of an epidural during delivery kind of freaked me out, too. I used it with the second, and boy am I glad I did!

[Duer 157099]

21. Just some notes about Enbrel...

I was just looking up it's history. I remember when Amgen bought out Immunex for their arthritis drug, which is what I believe this is.

What's interesting is that this study wasn't done by Amgen, and that no Amgen authors appear on the paper. I would think they would be taking the LEAD in studies such as this.

There's more to this story that needs to be dug out.....

edit to add link:

http://www.thestreet.com/tech/adamfeuerstein/10005480.html

[Tanuki]

22. The lead author, Edward Tobinick , owns stock in Amgen and has multiple patents,

both issued and pending, involving parenteral and paraspinal administration of enbrel in Alzheimer's and other neurological disorders, according to a disclaimer on page 18 in the original journal article as linked above.

[Duer 157099]

24. It would be interesting to see his investing timeline

Like, did he own the stock before he started the trials, or applied for patents, and since that time, has he purchased more, or has he sold some?

Was the stock purchased directly by him, or was it some sort of a stock option that he got from Amgen under some sort of arrangement?

Not that we'll really know these details, but they would be interesting.

[flowomo]

34. and the co-author has a yahoo e-mail address....

how weird is that?

http://www.jneuroinflammation.com/content/pdf/1742-2094-5-2.pdf

[melody]

26. any bit of hope against this kind of nightmare is wonderful

One study or not

[Duer 157099]

27. Wow, I just realized something mind-blowing

I've actually met the guy who discovered/invented this drug -- I didn't even realize it until now.

And now I have a family member who might very well get a chance to try this out.

Just a little trippy.

[momster]

30. Somebody Tell Terry Pratchett

recently diagnosed with an early-onset variety of this terrible thing.

Keeping my fingers crossed for everybody with an affected loved one.

[jwirr]

31. Any mention of side effects?

[Duer 157099]

36. It's a very well tolerated drug

Every drug has side effects, of course, but considering that this has already been FDA approved for arthritis, the side effects must be very minimal relative to the symptoms it's treating.

Besides, with AD, I can barely imagine a side effect that would be worse than the disease itself!

[gateley]

47. It was developed for RHEUMATOID arthritis -- and the only treatment before

the Enbrel breakthrough was basically chemotherapy.

They'll allow a few more side effects through for RA because it, too, is a debilitating disease.

I was working at a different biotech company on an RA treatment when Enbrel came out and blew most other treatments in the pipeline at the time out of the water.

There have subsequently been more RA treatments to come on the market -- I wonder if those might have an affect on AD, too?

[Duer 157099]

51. I don't really know too much about RA

All I know about Enbrel is that it's a soluble TNF-alpha receptor, so it just basically soaks up the TNFa in the blood. The other approach I've read about is using antibodies raised against the cytokines, is that what you were working on?

I guess any strategy that removes TNFa from the blood should be a viable strategy, and since inflmmation and cytokines seem to be implicated in so many diseases, there should be lots of info available.

[jwirr]

50. My mother had Alzheimer's so I realize that it is a blessing if it works.

I asked about side effects because it will probably be given to younger people than my mother when we begin to recognize the onset earlier.

[eowyn_of_rohan]

55. Whenever there is a medical breakthrough like this...

I think of the people who wish it would have come sooner. My sincere sympathy to you and your family. You ask a very good question, though, about potential side effects. They are pushing things through too fast and using us as guinea pigs. Hopefully this one will be different, but that is only wishful thinking.

[Dem2theMax]

63. I use Humira, another TNF blocker, and I have NO side effects at all.

I take it for psoriatic arthritis and for psoriasis. Both are totally under control. No more arthritic pain and not one single spot of psoriasis on my body. This drug has been a miracle for me.

I pray that it will work as well for Alzheimer's patients. My Uncle is one of them and I just sent this article to his daughters.

[Duer 157099]

69. Nice! How expensive is Humira, if you know?

Of course, it's an antibody so it might not be applicable to AD, but then again, it totally might. From what I can tell, there's a size difference, and the antibodies bind not only the soluble form of TNFa, but bound as well -- just don't know how that difference will relate to the AD research aspect, I'm sure they're asking those questions.

[Dem2theMax]

79. Expen$ive!

My insurance is charged $1,390 - AFTER they get a discount. That is for a one month supply. Two injections. For that price, I wouldn't be able to get it without insurance. My doctor had to fight like crazy to get the insurance company to approve it. We both had to jump through a lot of hoops before they would say "OK." In fact, she first tried to put me on Enbrel and they refused. So we waited a while, my arthritis got so bad I couldn't sleep, and then she asked for Humira. And they said yes. Go figure. But thank goodness they did say yes.

I've been on it for about a year and have had no problems with it at all. :-)

[Duer 157099]

83. Cripes!

It just makes me crazy to think that there are beneficial treatments that people will not get because of finances! Can you imagine trying to pay for that without insurance???

I know I know, this is nothing new... unfortunately. Maybe one day it will all be like a bad dream (after health care reform). Hope it happens in my lifetime!

[MissDeeds]

32. Do we dare hope?

I saw this insidious disease transform my grandmother, a once proud, dignified, loving lady into a shadow of her former self. She was the grandest person I have ever known, and to see her reduced to a state of confused helplessness was earth shattering. I try to blot it from my mind, but the memory remains. I hope this is not another pipe dream, but a true road to recovery for the millions afflicted with this cruel disease.

[TexasBushwhacker]

33. The thing that's great is that it's already FDA approved

Granted, it's not specifically approved for this application, but doctors prescribe drugs "off label" all the time. All it means for the manufacturer is that they can't advertise it for that use.

[pnwmom]

37. Which means that it's already undergone some safety testing, at least.

And doctors are allowed to use it as they see fit.

[Duer 157099]

35. Posting some more data here, for reference

Just to keep it all in one place, for reference sake.

Here's the earlier study done by the same group, from mid-2006. The difference in today's report seems to be the time frame of the improvement -- in the earlier studies, I don't think they documented the rapid relief of symptoms, so the possible mechanism could have been anything. This certainly narrows things down, and seems to really indicate that it's directly affecting something at the synaptic level, rather than being a secondary affect to something like mood elevation, etc.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16926764

I found it interesting that they chose the dose based on prior published findings when the drug is used for arthritis -- and I doubt the dose is administered the same way (no, not doubt, I'm certain of it!)

Even if this off-label treatment has increased risk of side effects, I think that for people who have AD, it's a risk worth taking. I mean, really, considering the option, I just can't imagine not trying it. I have little doubt that this has anything substantial to do with the real underlying cause of AD, so it's not a cure in any real sense

and an editorial of that paper is here:

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16926763

I would think that someone should be doing a study that looks at the incidence of AD in patients who have been taking Enbrel (or other anti-TNFalpha strategies) for other indications such as arthritis.

[AikidoSoul]

68. The article says it was administered via the spine

and that makes sense because it would get right into the CNS.

Are you saying that prior findings showed similar results using oral administration?

[Duer 157099]

72. I think it's only administered sub-cutaneously

I'm not sure, but I think that's what I've read -- for all of these TNFa antagonists.

There's another post downthread with a few more details

[Pierre.Suave]

52. Holy Crap

that is awesomer than awesome.

[lonestarnot]

54. Woohoo!

:woohoo: Most excellent!

[Love Bug]

56. I lost my mother to alzheimer's six years ago

I hope this turns out to be a good treatment!

[Duer 157099]

58. Some more interesting tidbits about the lead author

It's always interesting to speculate on the "back story" just like in any other field.

The author seems to have started publishing in 2004, and from the looks of his publication record, seems to be focused on finding other uses for Enbrel. Now, this may or may not mean anything relevent, just another fact to consider.

It could mean that Enbrel, since it does a very basic function which is to remove excess TNFa (tumor necrosis factor alpha, a molecule that's involved in inflammation among other things), has a wide range of therapeutic applications, and would explain why Dr. Tobinick applied for so many use-patents for Enbrel. That's the benign interpretation, and I'll not venture beyond that because I want to believe the best about people doing science :D

Here's his list of publications -- but there could be more that eluded my search criteria:

1: Tobinick E.
Paradigm Shift: Excess TNF-Alpha Emerges as a Key Therapeutic Target in
Alzheimer's Disease.
MedGenMed. 2007 Jul 20;9(3):17. No abstract available.
PMID: 18092024

2: Buell C, Tobinick E, Lamp K.
Resolution of chronic pain and fingertip ulceration due to hand-arm vibration
syndrome following combination pharmacotherapy.
Arch Dermatol. 2007 Oct;143(10):1343-4. No abstract available.
PMID: 17938362

3: Tobinick E.
Spinal delivery of p38: TNF-alpha inhibitors.
PLoS Med. 2006 Nov;3(11):e511. No abstract available.
PMID: 17132064

4: Tobinick E, Gross H, Weinberger A, Cohen H.
TNF-alpha modulation for treatment of Alzheimer's disease: a 6-month pilot study.
MedGenMed. 2006 Apr 26;8(2):25.
PMID: 16926764

5: Tobinick E, Vega CP.
The cerebrospinal venous system: anatomy, physiology, and clinical implications.
MedGenMed. 2006 Feb 22;8(1):53. Review.
PMID: 16915183

6: Tobinick E, Davoodifar S.
Efficacy of etanercept delivered by perispinal administration for chronic back
and/or neck disc-related pain: a study of clinical observations in 143 patients.
Curr Med Res Opin. 2004 Jul;20(7):1075-85.
PMID: 15265252

7: Tobinick E.
TNF-alpha inhibition for potential therapeutic modulation of SARS coronavirus
infection.
Curr Med Res Opin. 2004 Jan;20(1):39-40. No abstract available.

edit to add 3 more, not sure if they are overlaps or not:

1: Tobinick EL.
Targeted etanercept for treatment-refractory pain due to bone metastasis: two
case reports.
Clin Ther. 2003 Aug;25(8):2279-88.
PMID: 14512134

2: Tobinick EL.
Targeted etanercept for discogenic neck pain: uncontrolled, open-label results in
two adults.
Clin Ther. 2003 Apr;25(4):1211-8.
PMID: 12809967

3: Tobinick EL, Britschgi-Davoodifar S.
Perispinal TNF-alpha inhibition for discogenic pain.
Swiss Med Wkly. 2003 Mar 22;133(11-12):170-7.
PMID: 12715286

[thecrow]

60. What I'd give for a week of my father being "himself" again

This sounds terrific..... how much does it cost?

[Duer 157099]

61. As noted upthread, about $150-200 per week

but that's retail, and doesn't consider that it has to be administered by a physician -- it's an injection into the spinal area.

Definitely ask his physician about it, the more who know, the faster this moves along.

[Duer 157099]

62. Looks like there are 3 TNF antagonists currently in use

from wikipedia:

http://en.wikipedia.org/wiki/Adalimumab

Two are modified antibodies (infliximab/Remicade and adalimumab/Humira) while Enbrel is a modified version of the actual receptor of the TNFa molecule. Not sure how this impacts blood-brain barrier issues, or even if they yet know whether just a reduction in serum TNFa (as with sub-cutaneous injection) would also have an affect on AD symptoms (as opposed to delivering it into the spinal fluid as they did in this study).

Edit to add more details, just because I'm that geeky:

from http://en.wikipedia.org/wiki/Infliximab

According to product labeling, Infliximab neutralizes the biological activity of TNFα by binding with high affinity to the soluble (free floating in the blood) and transmembrane (located on the outer membranes of T cells and similar immune cells) forms of TNFα and inhibits or prevents the effective binding of TNFα with its receptors. Remicade and Humira (another TNF antagonist) are in the subclass of "anti-TNF antibodies" (they are in the form of naturally occurring antibodies), and are capable of neutralizing all forms (extracellular, transmembrane, and receptor-bound) of TNF alpha.<2> Enbrel, a third TNF antagonist, is in a different subclass (receptor-construct fusion protein), and, because of its modified form, cannot neutralize receptor-bound TNFa.

[NoodleyAppendage]

65. ONE PATIENT and one journal author has serious conflicts of interest.

Read the fine print at the bottom of the article for the interests of Dr. Tobobnick (sic).

How many times have we heard of encouraging CURES!, but then it washes out in the end.

J

[Duer 157099]

66. That's (sort of) true. BUT

Consider that, if the effects are obvious within minutes/hours of administration of the drug, not only to the patient and the doctor, but to family members as well... well, it's not like those cases where the doctor says "trust me, this works, just keep taking it for a few more months..."

I mean, this is a case of the proof being in the pudding, you know? If it works, and the only gauge of whether it works is the improvement in symptoms, that's a helluva place to start.

Again, it's not like this is a novel molecule that was just discovered in a lab and needs to go through years and years of clinical trials before people can try it.

Some times things *might* be just as they seem (in the good sense, I mean)

[NoodleyAppendage]

75. Cures the inflammation, but not the root cause of that inflammation.

I'm not trying to poo-poo this study...only cautious. The primary significance of the single-subject case study is the possibility that the dementia symptoms are positively related to inflammation moreso than the neurofibrillary tangles and amyloid plaques. However, it is the plaques and tangles that initiate the inflammation process, so this "cure" is really a way of improving negative cognitive symptoms and not reversing the extra-/intra-cellular processes that are causing the inflammation.

J

[Duer 157099]

76. Yes, agreed -- it only addresses the symptoms

Also, if you look at the study that they published in April of 2006 (http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16926764) they had a larger n (albeit still very small) and had similar results. From what I can tell, the main difference between that earlier study and this one was that this one, this case study, emphasized how rapidly the improvement occurred -- the subject was re-tested within hours of drug administration, which I don't think they did in the earlier studies.

[mopinko]

102. iirc, this was tried on chron's with no effect. chill out.

i agree this is a little inflated. these drug companies love to push the off label uses, as they have fewer hurdles. so they can run around with something like this- one patient- and scoop up the money.
this drug, last i heard, was also tried on chron's disease, which is basically RA in a different place, in the intestines, and it do not work.
take this shit with a grain of salt, folks.

[Duer 157099]

118. Crohn's is not Alzheimer's

But I'm sure I don't really need to point that out.

What if it works in AD because it specifically removes excess TNFalpha at the synaptic cleft which explains the cognitive effect? Is there a similar principle going on in Crohn's disease? Are Crohn's patients looking for relief in the area of cognitive improvement?

I mean, let's compare apples with apples, ok?

And to get technical, I think it's been shown that a specific form of TNFalpha, the transmembrane type, needs to be reduced for an effect in Crohn's patients, and since Enbrel only removes the soluble form of the molecule (the type found at the synaptic cleft, btw), although the monoclonal antibody versions of the drug also remove the transmembrane type, maybe that has something to do with it, too?

Just sayin'.

[mopinko]

123. and alzheimers is not ra, either. chron's is more closely related that az.

i'm sure i don't need to point that out. and one patient is not proof. i'm sure i don't need to point that out either. your "technical" points may have merit, or be bs. i don't know that much about it.
these kind of off label panaceas make a lot of money for drug companies. before the lawsuits stop them, usually a lot of desperate people get fleeced. can't think af a more desperate group than alzheimers patients. this thing smells like bullshit to me. maybe that's just me .

[Duer 157099]

126. It's not "one" patient - a prior (pilot) study was done witth 15

Results. The average age of our patient population was 76.7. The mean baseline MMSE was 18.2 (n = 15); the mean baseline ADAS-Cog was 20.8 (n = 11); and the mean baseline SIB was 62.5 (n = 5). There was significant improvement with treatment, as measured by all of the primary efficacy variables, through 6 months: MMSE increased by 2.13 ± 2.23, ADAS-Cog improved (decreased) by 5.48 ± 5.08, and SIB increased by 16.6 ± 14.52.

(emphasis added)

The whole paper is available, for free, online.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16926764

[Raine]

74. My father has alzheimers, I'm not holding my breath

for this, more "pie in the sky in the great bye and bye". x(

[goforit]

80. WOW!!!....this is a huge breakthrough!!! Hope Bush won't ban it!!

[Guaranteed]

82. This is enormous. nt

[Duer 157099]

84. Kickin' for the overnight crew

I'm thinking that this is something people should know about since it might be a relatively easy thing to ask a physician to consider trying this -- I know many of us here have friends and/or family members who are dealing with AD right now.

[BigBearJohn]

88. Thanks for posting this! K/R!

[Mark D.]

96. Prevention

This is probably why studies show high ORAC diets, particularly in anthocyanins that penetrate the blood brain barrier (Aronia Berry, Acai, Wild Blueberry, Black Raspberry, Elderberry, Boysenberry, Marionberry, Black Currant, from highest to lowest in this anti-oxidant) not only help the body, but the brain, as they pass the blood brain barrier and fight inflammation and free radical damage that can result in that inflammation, and do other damage as well.

I take Omega-3's daily. I use fish oil as they are more readily available in that than plant sources like Alpha Linoleic Acid (found in Flax, Hemp, and other nuts). Particularly the DHA, which is the single most important fatty acid of all, and of the two major Omega 3's (DHA & EPA) it is most valuable as it can be changed by the body into EPA (but EPA can't change into DHA). So get enough DHA and you are all set. Neuromin's is an algae based version and its purified.

Personally, I use Jarrow Max-DHA. Highest DHA per serving, best value of all fish oils. Also, it's molecularly distilled for purity, and consistently tested to have virtually no Mercury, PCBs or any other contaminants that are issues in whole fish or un-purified oils. It's also the only one I take that has no fishy aftertaste, or fishy tasting burps after, and I've tried every other kind of oil. This is fish body oil, superior to cod liver, as the latter has high levels of Vitamin A, so a healthy diet that gets enough could be at risk of A overload taking cod liver oil as well.

I also take twice the RDA of Vitamin D every day. Half in the morning, half at night. It's show that a dose like this reduces inflammation better than any other vitamin and not surprising, it reduces the risk of many kinds of cancer by 70-80% in various studies (just Google it). That and a high ORAC diet (dark chocolate, reservatrol capsules (hundreds of times more concentrated than wine, for far more benefits without the alcohol or fluoride (wine is highest of all foods in fluoride, grape juice is second and non-herbal teas, yes, even green tea, are third).

Personally, this better regimen/diet has greatly improved my memory, cognitive ability, math and problem solving skills. Being a musician helps too, as has been proven, to build new brain neurons and to improve cognitive ability and keep the mind active, possibly helping reduce decline risks. I also take 1000 mg MSM daily, shown to be anti-inflammatory. Natural methods are helpful and less expensive, and the side effects are coronary health, lower risk of cancer, and more energy.

I find I-HERB.COM has the best prices on Jarrow products. I personally take the liquid Max DHA which is most potent and good for those who don't like capsules. My girlfriend takes the capsules, twice a day, one morning, one night. They are smaller and easier to take than other large fish oil capsules, and again, per capita, more concentrated a source than other brands that I've tried. No, I don't work for either company, I just know what works and like keeping my mind sharp.

[JerseygirlCT]

99. Wow. Wouldn't that be something?

My grandfather died from this disease, and it's a horror. No one should have to live through that.

[Swede]

103. This is good news.

Let's keep our fingers crossed.

[colorado_ufo]

105. Some good news to start the day!

[Javaman]

106. I hope to god this is true. My mom is slipping away.

She still remembers me, but has no recall of my older sister. She talks in a 30 second loop. Every 30 seconds she repeats the same questions.

My mom is/was brilliant. She was a historian with a steel trap mind. Would do the times crossword in pen. Funny as all hell. Razor sharp mind.

Now I'm met from time to time with a blank stare, until she says my name. She still has such a wonderful smile.

Sometimes when I'm with her, I can't help but think to myself, I really miss her so much.

For hope for everything that is good in this world, I hope to god that this works.

Peace

[connecticut yankee]

107. That would be incredible if it works

My mother had Alzheimer's for about five years before she died.

It was so painful watching her deteriorate before my eyes. She didn't even know who I was.

I've been afraid that it's hereditary and I'll get it, too.

Maybe this is the answer.

[daveskilt]

109. Sorry to burst this bubble but....

Enbrel is a drug approved by the FDA for rhuematoid inflamtions and is approaching its tenth year (released for sale in 1998). After ten years the restrictions on generics lift unless a secondary or new primary use for the drug emerges. THe study refered to in this sciencedaily (which I had never heard of?) is from 2006 and showed only slight improvements in alzheimers patients. Amgen has made this type of leap before with its epoetin alfa drugs pushing them as wound healing drugs instead of kidney meds in order to stop the very expensive epogen/neupogen/procit drugs from being sold at much lower prices as generics.

It would be lovely to see effective alzheimers treatments, unfortunately Alzheimers, like other dementias, is degeneritive and progressive and while a reduction in swelling can alleviate some symptoms the underlying damage and progression of the disease cannot be reversed without regeneration of brain cells which is far beyond any current technology. Basically when its gone its gone.

Many of our patients here have seen improvement in symptoms with the use of anti inflammatories but the effects are temporary and not as great as the benefits of conventional (and cheaper) drug therapies such as aricept, respiradol etc.

[Duer 157099]

112. There's no doubt that drug companies can be so motivated

In fact, I'd be more worried that they may have had preliminary data but postponed it until the 10th year was approaching.

The thing is that it's not like there's no underlying logic in trying this -- it's known that TNFalpha plays a role in AD, so it's not irrational to think that decreasing TNFa levels might have a therapeutic effect in AD patients.

What's interesting is that I see barely any mention in the literature about trying thalidomide for the same reason -- believe it or not, thalidomide was approved in 2006 for use in multiple myeloma. As bad as the history was of this drug (thalidomide babies of the 1950s/60s), what if it turns out that it's a good match for use in AD? I mean, the major risk of the drug is it's teratogenic effects, but most AD patients are beyond the point of worrying about childbirth...

I don't think anyone is claiming this (Enbrel) as a cure -- it's a (potential) treatment for the debilitating symptoms, and as many in this thread have noted, for AD patients, for their families, that's a HUGE factor.

[McCamy Taylor]

113. You would need an intrathecal resevoir, right? Or a shunt to pump the med into

the brain. Unless you get spinal taps over and over again. So the cost would be much higher than the drug alone. There would be neurosurgery involved. And it would work best for those in the early stages--before brain damage. And the risks would be the same as for people with RA.

Sounds promising as a treatment, but from a public health standpoint a cure would be much better. This treatment could have horrendous complications.

[Duer 157099]

114. Dose is given once per week

the half life of the drug is about 5 days or so.

They still need to do tests to see if it can have an effect just by reducing systemic TNFalpha, so there's the possibility that it could be administered the same was as for RA (subQ).

Agree that a cure is much better, but damn if this isn't a really complex disease!

[Savannah_H]

117. how long before

how long before they tell us what the serious side effects are from the shot? A week, a month, never?

[Duer 157099]

119. There probably will be serious side effects

You can't just go around removing TNFalpha with impunity. I've read reports of people actually *developing* autoimmune diseases after treatment with TNFa antagonists -- and it makes sense because if you remove TNFa, you run the risk of actually causing the body to produce *more* of it (assuming there's a feedback loop somewhere, and where isn't there a feedback loop?)

It's complex, no doubt.

The question really is: is the improvement worth the risk? I'm inclined to believe that most people will say yes, depending on what the risks actually turn out to be -- and it could take some time to find that out, too, of course -- and again, some people will be willing to try it even knowing that.

[AikidoSoul]

127. What bothers me a lot about this expensive, off-label drug

"solution" is that it ignores the triggers of neuroinflammation that include many neurotoxicants. Neurotoxicants are implicated in many diseases but the emphasis is on treatment, not prevention.

Notable too is the fact that the same companies that make drugs, also manufacture neurotoxic pesticides, solvents, etc... profiting on both sides of this ever enlarging picture of toxicant triggered medical conditions.

[HannibalBarca]

120. Interesting

Entanercept is a soluble TNFalpha receptor, typically for rheumatic disease or other autoimmune conditions. Great to hear IF it pans out. There's big interest in these biologics for treatment of a wide variety of conditions, hopefully some of them work out. I believe memantine was another drug for alzheimers that has displayed some promise. The mainstay ach inibitors are only minimally effective if at all.

[Cant trust em]

121. Of course, the Journal of Neuroinflammation

It's next on my reading list right under the next issue of Guns and Ammo.

[SomeGuyInEagan]

124. And to think I let my subscription lapse!

Silly, silly me.

[cyr330]

128. Wonderful!

Alzheimer's Disease runs in my family-- my Grandfather died of it, and my dad is beginning to show early signs. I hope this is the start of something that will lead to definitive treatment for a horrendous disease. . . Especially BEFORE I get it!

[skip fox]

131. Fantastic. My father died of it plus congestive heart failure. Terrible death.

And I watch my memory all the time. (I make my living with my head, so loss of even a sizable portion of memory could lead to loss of world.)

[yurbud]

133. kick