Alzheimer's Treatment Mooted

aminorex writes "Enbrel (etanercept) has been immediately, markedly, and consistently effective in all Alzheimer's patients, according to a report in Science Daily. The original research article is available online at the Journal of Neuroinflammation web site. "We can see cognitive and behavioral improvement in a patient with established dementia within minutes of therapeutic intervention" comments one Journal editor." "All Alzheimer's patients" may be over-optimistic, but according to the article, though the research it concerns has been heavily focused on a single patient, "many other patients with mild to severe Alzheimer's received the treatment and all have shown sustained and marked improvement."

Comments

Bad Title

[Anonymous Coward]

Mooted... I do not think you know what that word means.

How about a study with n1?

[Ichoran]

I'm really not sure why this "study" was worth publishing. Where are the statistics of patient status after injection of drug vs. injection of drug-free control? How about a timecourse? Or anything besides anecdotes from one patient?

The hype on the article compared to what is shown is shocking. Even if the compound is a silver bullet that instantly and completely reverses Alzheimer's, you'd never know it from a paper like this. So this is an essentially useless bit of PR.

Re:How about a study with n1?

[Otter]

Also, this is a widely prescribed drug! It seems unlikely that it has massive, instantaneous effects on cognitive function that no one has noticed before.

As with the miraculous improvement in solar power efficiency in the next story, I'd love for this to work out but am not holding my breath.

Re:How about a study with n1?

[Anonymous Coward]

Also, this is a widely prescribed drug! It seems unlikely that it has massive, instantaneous effects on cognitive function that no one has noticed before.

I know it's wrong to read the article, but to work on Alzheimer's, the drug was injected into the spine. This is definitely an off-label use. Most likely, it doesn't cross the blood brain barrier. If this works, it might be possible to make a similar drug which can cross it.

Re:How about a study with n1?

[virtualXTC]

It isn't likely that AmGen would attempt to revise the structure of etanercept as they would then have painstakingly go back though every phase of clinical trials again with even the slightest modification. If they use the same product, they only need to complete Phase IIb (efficacy) and Phase III studies to market the drug for this now off-off label use.
While an injection to the spine may not seem ideal for patients, it would prove beneficial as there almost certainly would be many competitors to follow due to the fair number of other drugs that act on the exact same pathway. In fact, Embrol was actually originally developed as a rheumatory arthritis drug, targeting Tumor Necrosis Factor. (It has since been proven effective against many other autoimmune diseases.) While there are drugs like Remicade, Humira that also inhibit TNF, a positive result when using Embrol in Alzheimer's seems to implicate ANY drug that targets autoimmune disease as a possible cure.

Re:How about a study with n1?

[muridae]

It's also not likely that AmGen or Wyeth will work from Enbrel simple because it's a huge protein structure. 51234.9 g/mol is not tiny by any measure. Tweaking a protein to get through the blood brain barrier might not be the best way to go. This may be just a small part of the protein at work, or spinal injections might just be the simpler way to deliver it.

They could always re-patent some new delivery method, maybe a better diluent.

Re:How about a study with n1?

[Ichoran]

The issue is not about censoring a plausible idea. The question is whether highly hyped papers with extraordinarily little data are a good idea.

The problem with publications that have n=1 and consist of anecdotal observations is that they are highly unreliable. Since most "negative result" papers never get published, allowing unreliable anecdotes to be published leaves a trail of debris in the literature--you see various promising-sounding papers with no follow-up. You can surmise that the claims were probably false, but it could also be just that no-one was paying attention. It would be good if more negative-result papers were published, but until then, sloppy, unreliable work shouldn't be published in scientific journals. It's a distraction.

Log term effects?

[ArsonSmith]

Do we really want to put people on new drugs like this? What if in 40 years all these people come down with some kind of cancer?

Re:Log term effects?

[RetroGeek]

From the original article:

potential risks of etanercept, including infection, cytopenias, possible increased risk of lymphoma and demyelinating disease, death, eye inflammation, and congestive heart failure;

Re:Log term effects?

[geminidomino]

Not sure if you're kidding but aren't most Alzheimer's patients old enough that 40 years down the road isn't a big concern for them?

Re:Log term effects?

[vux984]

Do we really want to put people on new drugs like this? What if in 40 years all these people come down with some kind of cancer?

Do the math.

I think a 75 year old diagnosed with alzheimer's wouldn't blink at taking a chance on that. Coming down with cancer at 115 is not going to impact him much. He'll probably have died 15-25 years prior.

And I think even a 35 year old diagnosed with alzheimer's would probably take that chance. Choosing cancer in your 70s vs severe dementia by 40... its not a call I'd find hard to make. I'll take the 'cure' thanks. And maybe 40 years from now they'll be able to control the cancer too.

Re:Log term effects?

[WillAffleckUW]

Is there a single person with Alzheimer's Disease and a life expectancy > 40 years? Somehow I think that's an acceptable risk.

No.

The average person with Probable Alzheimer's Disease status (there is no such thing as certain, until we take your brain and slice it and stain it, actually) has a life expectancy, even if they got early onset AD at around age 40, of at most 20 years.

Re:Log term effects?

[Danse]

Do we really want to put people on new drugs like this? What if in 40 years all these people come down with some kind of cancer?

Do the math.

I think a 75 year old diagnosed with alzheimer's wouldn't blink at taking a chance on that. Coming down with cancer at 115 is not going to impact him much. He'll probably have died 15-25 years prior. Slasdot. Where everyone plays the straight man, without even realizing it.

Re:Log term effects?

[Valdrax]

I know you're joking, but I'll take cancer over Alzheimer's. Even if the drug directly caused it. I may die in miserable pain, but I'll die as me.

Alzheimer's and growing old

[LithiumX]

For all the medical problems society obsesses over treatments for (cancer, aids, and other popular areas), Alzheimer's (and senility in general) is the one that scares me the most. I would rather die in pain, with my mind intact, than slowly forget who I am.

My paternal grandmother died before Alzheimer's was well recognized, but in retrospect it's pretty likely to be the cause of her condition. My grandfather, having seen his wife forget who he was, was always far more afraid of going down that same path than he was of his own approaching end - and I can easily see his point.

The worst part about growing old isn't physical frailty... it's the slow breakdown of cognitive power. Of course, as a 33-year-old I can say this with absolute authority. The worst part of *that* is that it doesn't wait to start until you're old, either. I'm sure most of you have noticed changes over the years, and not all of them good.

Here's a question that's been on my mind lately. How would most of you rate changes to how your mind has worked over the years? Have you noticed your reflexes aren't what they were when you were a teenager? Looking at any older writings of yours, have you ever had the feeling that your imagination may have grown more refined, but also lost some of it's raw power at some point? Regardless of the cognitive rewards of time and experience, are there any earlier capabilities that you feel you may have lost some grip on, or even noticed more clearly in younger coworkers or relatives than you used to?

In my case, for example, I've noticed that in a video game, I just don't react to unexpected situations quite as fast or well as I used to. I remember charging into a room in Doom, blasting everything I saw and dodging almost every shot - whereas lately I tend to get hit more often - I don't do the duck-and-dodge like I did in my teens and early 20's. On the other hand, I'm much more calculating in every move I make, and find it easier to manipulate computer opponents than it used to be - even with all the advances in AI. I don't have the raw speed and reaction time that I used to, but the intellectual component comes more readily and with virtually no effort compared to before.

What do you younger guys think of the minds of older coworkers? What about any of you in your 30's and 40's, in dealing with people younger or older than you on an intellectual level? And of the most interest to me, how do you geezers (I know there's some who come here - maybe even a handful) relate to us 30-somethings? Do we seem like slightly inexperienced versions of your peers? Or do we seem like idiot children with fast reflexes but weak comprehension?

Re:Alzheimer's and growing old

[another_twilight]

From personal experience I tend to 'learn' a response to certain situations (patterns of AI in games for eg). The first few instances are all reaction, but as time goes on it starts to become stimulus-response. I suspect that as you get older you accumulate a larger set experiences from which you can draw - simultaneously giving you a greater depth and refinement to your response, but requiring less and less pure reaction.

What you don't use, you lose. I dare say that just as physical fitness, which used to be so easy in our 20s now requires more effort to maintain, so too mental flexibility, responsiveness and reaction.

Anecdotally, I have not yet observed a degredation in raw reaction (late 30s), but I have been fairly agressive in making sure to constantly find things that require that I use/exercise this. Try learning a new physical activity/sport (and then another in a year or so). Find new ways to play games - yes, you can out-think your AI opponent, so how about playing with pistol/s only? No save/restores?.

It may be that the comparison to physical fitness/conditioning is a poor one and it is simply a matter of maintaining a 'familiarity' with novelty so that my brain doesn't insist on trying to find a learned response to use in every situation. Perhaps it will all catch up with me shortly, and/or my self-perception is more distorted than I have allowed. YMMV.

Re:Alzheimer's and growing old

[QuickFox]

Regarding your theory, I think it may be spot-on, I seem to remember reading that studies have shown precisely this, that men with more frequent ejaculations run less risk of prostate cancer.

Regarding the very sudden disappearance of your sex drive, I think you should explore the cause, because it may be an early warning about far more serious problems building up without you noticing.

I think the suddenness indicates that it very likely it's due to (possibly unnoticed) severe stress. In that case the stress may be slowly damaging you severely, even though you may not notice the stress at all -- this can happen while you feel wonderful in all respects. Thus it might be a good idea to see a psychologist or psychiatrist, whatever the appropriate therapist is called in your country (the terminology varies). There's a lot you can do to prevent stress-induced deterioration just by seeing the right expert and learning a few methods. A specialist on Cognitive Behavioral Therapy would probably be ideal.

If stress is not the cause, several other possible causes would be urological, although in that case I would expect the change to be gradual (but I'm no expert). Then it would be a good idea to see a urologist. There are also lots of other possibilities, such as drugs, blood system, neurology etc, but your urologist should know all these possibilities, and can send you to the right expert if necessary.

Re:Alzheimer's and growing old

[CharlesEGrant]

The worst part about growing old isn't physical frailty... it's the slow breakdown of cognitive power. Of course, as a 33-year-old I can say this with absolute authority.

I'm sure circumstances vary widely, but my experience is just the opposite. In the last few years my wife and I have lost all four of our parents: hers to heart disease and Parkinson's, mine to heart disease and Alzheimer's. None of them is a picnic, but from what I saw, Parkinson's was a much harder road then the others. The initial diagnosis of Alzheimer's was devastating to my mother, but as the disease progressed she lost track of the fact that she was severely impaired. The world became a very confusing and sometimes frightening place for her, but death and suffering no longer loomed over her. Life was lived minute to minute. Some minutes were good, and some were bad, but they never lasted very long, and there is some comfort in that. My father-in-law had a Parkinson's like condition and retained his mental acuity to the bitter end. For three years he could fully appreciate the gradual process of being buried alive in his own body. He bore it stoically, but you could see how frightening it was.

By contrast, the deaths from heart disease were traumatic, but quickly over.

Re:Alzheimer's and growing old

[Magada]

Still unsure if you're a troll, but... the statistical corellation between the frequency of ejaculations and prostate cancer likelyhood is well-documented. Sex is good for you, even if you do it one-handed!

Just In Time for Terry!

[Dunx]

With any luck this treatment will be (a) effective enough, and (b) available enough in the UK for it to have a positive effect on Terry Pratchett's condition.

Re:Just In Time for Terry!

[DarkGreenNight]

So, I see that the plan has worked:

http://somethingpositive.net/sp12232007.shtml

(Hopefully this will be the start of a good treatement to all those afflicted by this disease)

actually, they do

[BitterAndDrunk]

But it's an annoying fucking word, because its two meanings are actually opposite of one another:

1. To bring up as a subject for discussion or debate.

2. Of no practical importance; irrelevant.

Very obnoxious word that way.

Re:actually, they do

[Jhon]

1. To bring up as a subject for discussion or debate.
2. Of no practical importance; irrelevant.

Seeing how effecient and successful the UN runs, I think perhaps you could read that as "To bring up as a subject for discussion or debate is of no practical importance and irrelevant".

Glad we cleared that up.

Re:actually, they do

[stonecypher]

You're not entirely correct. You've taken one correct meaning and split it into two incorrect halves, then ratified the second half by confusing conjugations.

The verb "[to] moot [something]" is to raise an issue for the specific purpose of displaying it to be unimportant; this is the sense in which the article uses the word. Mooting something is an active and target-specific process whose intent is to weed out irrelevancies. If you have done either 1 or 2, but not the other, you have not mooted something. There is only one meaning, and it is not internally inconsistant at all.

Meaning number two is also the way the past tense adjective is spelled/pronounced. However, it is common in English to have an action and its result adjective be the same, despite that the result adjective represents only the end state of the action: I shot him, he was shot; what you've suggested is to point out that shot has two meanings, one to engage in the act of shooting someone, and also two, to be in the state representing having been hit by a bullet. The verb and its past tense correlated adjective are simply frequently structured thusly.

It's interesting, though, that this divide should seem apparent.

I would take this with a grain of HCl

[WillAffleckUW]

The scientific discussion is still ongoing, IMHO.

The problem mostly is that we're still dealing with symptoms and not with the underlying mechanistic fault that causes AD.

For example, we're investigating various drugs that remove plaque in the brain, but the problem arises that we don't have anything that actually corrects the mechanism which creates the plaque in the first place. And most of the treatments are moderately risky so far.

Re:I would take this with a grain of HCl

[Hatta]

You might like some NaOH to go with that HCl.

Re:I would take this with a grain of HCl

[DirkGently]

...for those of you that had chem at 8am on a monday, when you combine those two you get salt @ water. I just had to point that out because I thought it a particularly funny nerd-joke and I didn't want anyone to miss it.

One patient? Competing interests?

[a_d_white]

While the basic biology seems sound, this result is from only one patient while one of the authors holds stock in the company that manufactures the drug and has applied for several patents for its use in treating Alzheimer's.

Pardon me while I await the large sample, randomized controlled double-blind study by authors with no competing interests to confirm these findings.

Results of a few minutes of work

[Wilson_6500]

My two-minute Pubmed screening (dinner's getting cold) shows that it seems that this guy's more recent papers, at least, are all technical note-like submissions in online journals. He also has some noted conflicts of interest. However, there is one pilot study. I don't know if this link will work without going through Pubmed, but this is a year-old pilot study that is probably not the one referenced in the article. They basically conclude, like so many other pilots, that the treatment is promising but needs more rigorous study.