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Drug Halts Decline In Alzheimer's Patients
Posted by
kdawson
on Wed Jul 30, 2008 07:16 AM
from the now-i-rember dept.
from the now-i-rember dept.
ljw1004 writes "Alzheimer's researchers are divided on whether the disease is caused by 'beta amyloid' (a peptide found in Alzheimer brains) or by 'tau protein' (normally used for cellular scaffolding, but can aggregate out of control and destroy neurons). Today in Chicago a new drug has been announced that stops tau aggregation and appears to have halted Alzheimer's-related decline in 300 clinical trial patients. The drug is known as 'rember.' Do you have friends or family who appear to be on the road to dementia? Here is an online questionnaire, part of one used in the clinical trial to diagnose dementia. (Disclosure: I made the online questionnaire, and my father is one of the scientists behind the drug.)"
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Rember (Score:4, Interesting)
Is that a deliberate pun on 'remember'? :?
Re:Rember (Score:5, Funny)
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Re:Rember (Score:4, Funny)
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Re:Rember (Score:5, Funny)
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The underlying facts don't seem funny. (Score:4, Informative)
1) The person who submitted the story to Slashdot says, The trademark word "rember" is written with a lower-case initial letter [slashdot.org]. A trademark in a proper noun, and must be capitalized to show that it is not a common noun. The word seems to me to be chosen to confuse those who don't know how to think about drugs in a scientific way.
2) The "drug" is an aniline dye commonly used in laboratories. Aniline dyes have been known to cause cancer. See the comment about that, Odd facts about the BBC article [slashdot.org], which I posted below.
3) The Slashdot story is an advertisement, apparently. The company is looking for money for more trials. See the comment More odd facts about the drug "Rember" [slashdot.org].
4) The above comment links to a Chicago Sun-Times newspaper article which says that two-thirds of the study produced no results and were ignored. The one-third of the study which is being considered produced only "7 percent" results.
5) The chemical in the drug is cheap and has been widely available for decades. Apparently to make it commercial, they are claiming they have a special formulation.
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Re:Rember (Score:5, Funny)
That's probably the real reason Fermat never finished his last theorem.
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Re:Rember (Score:5, Insightful)
For clarity and completeness I should add:
This is awesome news. My grandfather is suffering from an advanced state of this disease and it's horrible to see in what state he currently 'lives'.
He does not recognize me, or my brothers, or my parents (inc. his own son!).
Perhaps my first post (parent) sounded like I did not take this seriously. I guess it's more of a coping mechanism that got in action.
To all the scientists: please keep up this wonderful work! It'll probably be too late for my grandfather, but no-one should have to suffer like.
I hope that it won't be long before it helps to save many lives from being destroyed.
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Re:Rember (Score:4, Insightful)
"He does not recognize me, or my brothers, or my parents (inc. his own son!)."
This just goes to show us how important our memory systems are in our intelligence and what an important role it plays in our lives.
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Re:Rember (Score:5, Insightful)
Unless you recently fired a bunch of US Attorneys, in which case losing your memory can be extraordinarily helpful.
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quite the opposite (Score:3, Insightful)
Actually, watching someone with advancing (but not yet devestating) Alzheimers can also show you how little memory is needed for intelligence. People can continue to cope in social situations for quite a while operating almost statelessly to guess at how they should behave. Only when you pay close attention do you realize the serious short-term memory deficit.
Re: (Score:3, Informative)
The late Sir Martin Roth, a leading UK psychiatrist, always used to insist: "Alzheimers is NOT a disease of cognition". It has two separate components: the loss of personhood, and the loss of memory/cognition. In the questionnaire, one of the questions that best correlates with the onset of the disease is "... and for how long have you been depressed?"
Re: (Score:3, Insightful)
That's the stage I had the most problems with when my grandfather had Alzheimers'.
When he got to the stage where he thought he was a little boy again, he was much more cheerful. Again, for the family it was no pleasure to see that, but he had the time of his life
Re:Rember (Score:5, Insightful)
First of all I understand completely what you're saying and to a certain extend that is true.
But on the other side, his body is starting to fail and he is suffering from that. "Gradually, minor and major bodily functions are lost" as Wikipedia describes it [wikipedia.org].
It's getting somewhat better now, but recently he could barely breath, general pain all over his body and basically unable to swallow, combined with a cough he developed. He could not even eat Apple mush when helped.
Every now and then he has a 'good moment' and suddenly he can say more than 5 words without falling asleep again, but the general condition is suffering for him.
I know this could sound weird to some, but every time he closes his eyes I just hope that he drifts away to a better place and stays there.
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Re:Rember (Score:5, Insightful)
I don't mean to hurt your feelings, but I do work in health care, on a Memory Care Unit, specifically. The MCU is designed for people with many forms of dementia, our most common diagnosis being Alzheimer's. I am sure you know many of the ugly symptoms of this disease. Confusion, loss of memory, loss of fine motor skills, deteriorating ability to perform activities of daily living, eventual death, etc. This drug may sound like a godsend, but think about it for a moment.
If your loved one breaks down crying several times a day because he or she can't tell where everyone is or where they are, if he goes into violent rages because he thinks he is being held against his will, if he lives in a constant state of fear because he knows something is wrong but he can't figure out what it is, if he tries day after day to go home but his captors refuse to et him go, causing him to fear for his life... do you really want a drug that will keep him in that state, somewhat permanently?
At best, wait until the affected person progresses to a state of Alzheimer's that is more comfortable for him or her -- around stage 5 (out of 7 total) people forget that something is wrong and they happily live their lives in total confusion. Then start the drug therapy. But stalling people's progress in a state that makes them absolutely miserable is not a miracle drug's miracle cure. It's torture.
Check out http://www.iatbdementiacare.com/index2.html [iatbdementiacare.com] I worked with the guy who runs the site and wrote the book on Dementia Possible Care. He is crazy insightful and smart when it comes to caring for people with Alzheimer's. Trust me, the $20 for the book will serve you tremendously.
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Re:Rember (Score:5, Insightful)
No, definitely not. You raise a valid point and I understand it completely.
My parent post should be seen more in the light of 'progress IS finally being made'... perhaps one day we can label it a disease that can be prevented.
Not just for 'everyone out there', but I have to admit also from a slightly selfish perspective:
My grand father was a fish salesman for his entire life. All the Omega 3 fish oil he has ingested wasn't enough to prevent it.
Then there's my father. We (mother, brother, me) are not sure if it's his current stress level, but in the last few months he is less 'sharp' than he used to be and his memory does fail him every now and then.
He's 57 and the idea alone that he might be heading for the same road is very terrifying to say the least.
And my brother and I are also starting to fear that we might have inherited a genetic disposition for this disease.
Personally I love learning.. I'm an addicted to knowledge and I'll pick up a book in bed even if my body is almost robbing me of my consciousness by force.
The idea that 'everything that I am' might one day start to slowly degrade freaks me out. Euthanasia is a word that comes up in this context if this situation might start to become a reality in a (hopefully) very distant future.
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Re:Rember (Score:4, Insightful)
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Re:"Rember" is methylthioninium chloride? (Score:5, Insightful)
In what way is this not science? Hypothesis 1: Compound A is effective against disease X. Falsified. Hypothesis 2: Compound B is effective against disease Y. Falsified. Hypothesis 3: Compound C is effective against disease Z. Not falsified. Perform double-blind tests and find a dosage that is safe and effective. Sounds like science to me.
How would you conduct a search for safe and effective drugs? If you have a better way, I'm sure pharma companies would be all ears!
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So what's your point? (Score:4, Interesting)
There are two schools of thought in drug research. One is to throw lots of stuff at the wall to see what sticks, and the other is "intelligent design," using extensive modelling and simulation to build molecules on spec. So far, the former school is ahead about ten thousand to one.
If you had syphilis in the early 1900s, would you balk at taking Salvarsan just because it contained arsenic, and because the guy who came up with it was on his 606th try? Well, we're in exactly the same boat now with respect to Alzheimer's.
4) "... the trial was funded by a pharmaceutical company..." according to the BBC article.
And they're getting results. What do you value more, your money or your sanity? If you get this particular disease, you (and your family) are going to be damned glad somebody came along and offered you the choice.
If you have a better process in mind, we're all ears. So far, the more-socialized European approach has given us, well, LSD.
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Re:"Rember" is methylthioninium chloride? (Score:5, Informative)
I should say that Claude Wischik thinks he *does* know what causes Alzheimer's disease. He's sure that tau tangles cause it. He's spent the past twenty years accumulating evidence and trying to convince people of the fact, but it's been hard because of the entrenched scientific dogma that amyloid causes it. The success of this drug finally is a vindication.
You're absolutely right, though, it was a case of trying lots of chemicals. At least, the larger pharmeceutical companies have been trying hundreds of thousands of chemicals from their libraries. A smaller company like TauRx can only manage far fewer.
But what's needed is a test-tube test to judge whether your chemical works. Previous attempts have judged whether their test chemicals work to prevent Amyloid buildup, and so they skip right over the useful ones. Claude Wischik realised that the test-tube test should be judging whether a drug works on tau tangles. This test-tube assay was the first key invention.
After that, you need an animal test to judge whether the drug works in animals. The second key invention by TauRx is a transgenic mouse where you can make it selectively express tau aggregates. They created mice with alzheimers, watched them make their demented way around water-tanks looking for firm ground, and then showed that Rember improved their condition.
You're right to ask about the temporary remissions. The clinical trial lasted 19 months and had 321 patients -- not a short trial! The test results had a p-value of 0.2%, i.e. there's a 0.2% chance that the improvement was due to the common random fluctuation rather than the drug's effect.
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Re: (Score:3, Funny)
"The drug is known as 'rember.' "
Too bad even though it stops Alzheimers, it causes dyslexia...
Wow, that's awesome (Score:5, Insightful)
Re:Wow, that's awesome (Score:4, Insightful)
It's hard to think of a scarier disease than one where you slowly lose your mental faculties.
Ebola [wikipedia.org]
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Re:Wow, that's awesome (Score:4, Interesting)
Let me see: On one hand I have a disease that gives me a rather quick (even though painful) death, and on other I have something that slowly turns me into a vegetable. Tough choice? I think not.
If I was forced to pick one (without a hope for cure once I made my choice) I would pick Ebola any day of the week. Thank you very much.
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Re:Wow, that's awesome (Score:5, Interesting)
Personally I'd still rather that, than not recognise my daughter. I'd also rather put my loved ones through a relatively swift and dramatic end to my life, than a very slow, gradual decline, in which I am effectively dead to them (as I don't know who they are) long before I stop breathing or moving around.
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Re:Wow, that's awesome (Score:5, Interesting)
Haemorrhagic Fevers are bad, but not as bad as the public seems to paint them. Films such as Outbreak, and books such as Richard Preston's Hot Zone have made it seem like Filoviruses and other haemorrhagic diseases kill you in a matter of hours and cause you to have to be buried in a water-tight plastic bag. This is about as accurate as saying cancer patients are going to mutant into something that looks like a Horta due to out-of-control cellular replication.
For Ebola in particular, there are methods of treatment, including a post-exposure vaccine that has shown to be 99% effective in monkeys. The only downside is that it must be administered very quickly, or there will be too much damage already done to the patient (within 4 days.)
I can thinking of many ways of dying that are far more agonising that Ebola. MS would be one. To be gradually robbed of my motor and mental skills would be a horrible and terrifying experience. As someone who recently lost a family member who suffered from senile dementia (and whose dementia was directly responsible for her death), I can say that it is definitely worse for the sufferer than for the family. As painful as your loved one not knowing who you are is, it is far more painful for them, and to watch them, come back to moments of lucidity, only to have to have where they are and what has happened explained to them yet again.
I think it is a sign of the times that people seem to think that physical agony can even begin to compare to psychological agony.
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Re: (Score:3, Funny)
Judging from the number of spelling errors in the above post, I think it's safe to say that I am already being gradually robbed of at least one of my cognitive functions.
Re: (Score:3, Insightful)
I think it is a sign of the times that people seem to think that physical agony can even begin to compare to psychological agony.
On the contrary, I think it is only a recent development that we can see psychological pain as being as real or more real than physical pain. It is not so long ago that mental problems were casually dismissed by most as being 'just in your head'.
The point I'm trying to make is that modern society is improving in this regard, rather than degrading.
Re: (Score:3, Insightful)
Apparently you've never talked to any one of the large number of men in America who saw combat in either World War II, Korea, Vietnam, or any of the other myriad police actions we've been involved in. I think the older generations are very well aware that there are things worse than painful death; being the one who didn't die can be a horrible, horrible experience.
Anyone who grew up in the 20's or 30's, or the 40's or 60's and 70's and saw the wounded who returned home, missing arms and legs, hands, eyes,
Re:Wow, that's awesome (Score:5, Insightful)
Its nasty, I worked in Alzheimers care for years.
What's worse is the routine treatment of Alzheimers patients with anti psychotic drugs, Most of my time as a nurse in that field was spent undoing the damage caused by such ill advised prescribing of chemical straight jackets to deal with minor behavioural issues.
If this drug can stop Alzheimers from getting worse once diagnosed I'd be happy, both professionally, and selfishly (I want Pratchett on this stuff NOW).
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Re: (Score:3, Interesting)
He suffers from Alzheimer's Disease. She has it! (Score:4, Interesting)
Although Alzheimer's Disease might seem a very scary disease, the reality is often that the family members suffer most. As a partner of someone with Alzheimer's Disease, I can affirm this. Although my wife is only in the early stages of the disease, the effects are already dramatic. She is no longer my equal and I often feel I have to treat her like a teenager, as she is showing similar kind of behaviour. Our teenager daughter is also suffering from not having a "normal" mom anymore.
Although most people with Alzheimer's Disease go through periodes of depression, they often appear to be rather happy with their condition, because they are no longer aware of what has happened to them. They forget that they forget.
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Obligatory (Score:3, Funny)
Now what's that drug called...?
Video games... (Score:4, Interesting)
Thank your dad for his research for all of us - this is one of the worst ways to go.
Disclosure: I made the online questionnaire... (Score:3, Interesting)
BTW if you want to get into the fun stuff answer question 1 incorrect and question 2 correct and hit submit.
On the sad side if you answer questions 1 and 2 correct and then forget the rest of the questions you don't get hit with having some dementia and just a boring all is probably fine screen.
Rember is Methylene Blue (Score:5, Informative)
Andy
beta amyloid (Score:5, Interesting)
Re:beta amyloid (Score:4, Informative)
I am not a Doctor (for a couple more years), but...
I think that Alzheimer's is probably a confluence of different things instead of just a single disease. It could be that the plaque build up does not directly cause Alzheimer's, but that it creates an environment more conducive to the real disease agent's functioning. Or it could be that they are both expressions of an underlying pathology that as yet escapes us -- they're found together not because one causes the other but because they're both caused by the same thing.
I remember seeing some research a few months ago that showed that treating Alzheimer's patients with drugs to increase insulin sensitivity seemed to have some benefit, suggesting that the disease could be a third form of Diabetes.
I really do wonder if it should be Alzheimer's Syndrome instead of disease. It seems that there are several different causes of the condition, at least for the moment, which either contribute to the degeneration or could be the direct cause.
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Re:beta amyloid (Score:4, Informative)
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Somebody get hold of Pratchett (Score:3, Insightful)
He was looking for a high-end brain specialist in neurochemistry at last report. Subby's dad fits the bill.
Re: (Score:3, Funny)
I went to the library to do some research regarding a cure for Terry, but all I got was a banana.....
Is it patentable? (Score:4, Interesting)
Wikipedia [wikipedia.org] also notes:
Which raises the question, is it patentable? TFA notes that the study was funded by a pharmaceutical company, but I am worried that the funding will end when the company discovers that the drug won't be profitable.
Probably has something funky done to it (Score:3, Interesting)
One of the toughest problems when developing drugs for the brain is crossing the "blood-brain barrier". For instance, neurotransmitters will not cross the barrier, so we can only prescribe drugs that affect them, as opposed to prescribing doses of neurotransmitters themselves.
I am 100% sure this is patentable, it is not as if nobody knows about methylene blue; and possibly they have patented a way of getting the drug directly into the brain.
But yes, unpatentable drugs are a real big problem. One of the dr
Who cares? It won't be free to everyone (Score:3, Insightful)
This is just another huge money grab for big pharmaceutical companies. Why should you guys get to make any money off of this? All you did was cure Alzheimer's disease. Why should rich people get to avoid dementia when the poorest can't afford it? Shouldn't everyone get dementia equally?
When are we going to stop these big rich drug companies from making these obscene profits for merely curing diseases and plagues?
[Evil socialism off]
I actually hope you guys succeed and make billions. If I get Alzheimer's disease someday, it's nice to know there might be a cure, even if I have to pay you for your effort to find it.
Alzheimer's Research even worse than mentioned.... (Score:5, Interesting)
What gets me is that 3 years ago, people found a direct link between HHV1 (Herpes Simplex 1 - the kind you get coldsores from), and Alzheimers; literally, the plaques are riddled with the virus.
Add into the mix the fact that new hi-res MRI devices show microbleeds all over the brain of most people, and that these break the blood/brain barrier in those areas, and it gives a very simple mechanism for the virus to get into the brain (even if it doesn't just travel up the neurons themselves).
Why are people focusing on the plaques and the tangles? We have a virus here that lives inside of neurons, which has been found and strongly correlated with the disease.
There are other classes of herpes virus which have similarly been implicated in brain cancer. This should be a big fat red X marks the spot. But most researchers are too specialized.
Dementia != Alzheimer's (Score:5, Informative)
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Re:tested? (Score:5, Informative)
Phase 1: safety at various dosages
Phase 2: small test of efficacy and determining proper dosage
Phase 3: larger test of efficacy
It is still years away from the market. There was a screw-up in the formulation of the highest dose in this study, and the lowest dose had no effect, so only the middle of three doses tried had any effect. I found that out here [suntimes.com]
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Re:tested? (Score:5, Informative)
See this [wikipedia.org]
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Re:How is it administered? (Score:4, Informative)
It was administered in pills. The world's supply of methylene blue largely comes from a factory in china, but TauRx wanted much higher purity for their drug, so they invented a new process for manufacturing it and oversaw production in a new factory. The methylene blue is put into pills and taken orally.
There were difficulties with formulation. It had to do with the problem of getting the right dose to the brain, and not having it get digested. Also there was a problem (I can't remember which way round) about acid/base conditions. Maybe it was that the stomach acid wanted to oxidise the drug, so it had to be mixed with a reducing agent so it lasted long enough to reach the brain? I'm afraid I worked on the questionnaire side, not on the chemistry....
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Re: (Score:3, Funny)
Yeah. And mine said I have no signs of dementia. Clearly this test is fubared!
(why do I have to wait 7 mintues between posts)?
Laughing is FORBIDDEN! (Score:3, Insightful)
Shame on you making jokes about this dreadful disease.
My dad seems to have Alzheimer's - he now lives in a veteran's home, often doesn't know who his kids are, or that he has any, who his wife is, etc. It seems like his greatest point of clarity is that he doesn't want to be in the home, so we have to make excuses every time we leave there without him. Plus he had some recent dental issues (all his upper teeth are falling apart) - my mom arranged for him to get dentures, but he had a habit of taking them out and now he's lost them. She won't be getting him