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Drug Halts Decline In Alzheimer's Patients
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.)"
Is that a deliberate pun on 'remember'? :?
While the article says that the disease was halted in 300 trial patients, it's not quite clear that the effects of the disease can be reversed. So those in the early stages have perhaps gotten their lucky break, but many who have already progressed down the road to lunacy are still without reprieve.
I'm glad to see such progress being made, and more importantly that aluminum cans and deodorant have been vindicated. Seriously though, I'm turning Japanese isn't just a song anymore, it's a long gone daddy in the USA. Where some patients may get a chance to return to normal lives, it's still a bit sad that those who have lost loved ones to the waking death of Alzheimer's will only feel a bitterness that this trial was conducted so long after they bore the brunt of it.
Your dad is doing good work. We need more people like him.
It's hard to think of a scarier disease than one where you slowly lose your mental faculties. I'd take almost any other disease over Alzheimer's.
Tic-Tac-Toe, Global Thermonuclear War, and relationships all have the same winning move.
Now what's that drug called...?
Odd thing about Gen-xers and the following generations...due to our proliferation in playing video games, there won't be as many of us with Alzheimer's, but EVERY one of us is going to wind up with carpal tunnel.
Thank your dad for his research for all of us - this is one of the worst ways to go.
It's important to remember that Dementia != Alzheimer's. Alzheimer's can cause a form of dementia (Alzheimer's-related dementia), but dementia has many other causes, some are age-related and some are not.
My blog
(Disclosure: I made the online questionnaire, and my father is one of the scientists behind the drug.)
oh yeah, well my dad...
So let the complaints on the code begin.
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.
Andy
This drug is in the second of three phases which are required prior to FDA approval.
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
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)?
See my journal for slashdot ID's by year. Mine created in 2005. http://slashdot.org/journal/289875/slashdot-ids-by-year
Except that in this case you can skip all that and do a little experimentation on your grandparents. This is not a new drug: it's plain old methylene blue, which has been used for all kinds of purposes for a century (from anti-malaria drug to aquarium antifungal)
See this
(I'm a PhD Neuroscience student) It seems like more and more scientists are moving away from the beta amyloid plaque buildup hypthesis. While it seemed like a great lead, people who die with no symptoms of dementia or Alzheimer's Disease can still have a buildup of beta amyloid plaque as massive as the person who did die of Alzheimer's. It could be that high levels of beta amyloid plaque buildup increases the risk of getting Alzheimer's, though. It's a hard disease to crack, that's for sure. If this new drug really does work, it'll save 5 million lives a year, and that's just in the past few years; as the Baby Boomers all get past 65 we're going to start seeing a massive increase in Alzheimer's Disease.
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.
He was looking for a high-end brain specialist in neurochemistry at last report. Subby's dad fits the bill.
The next Slashdot story will be ready soon, but subscribers can beat the rush and slashdot the links early!
Wikipedia 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.
One of our competitors trademarked the term "hypothesis". From now on, we will call them "boneheaded ideas".
Too bad for the editors this won't be available for a few years.
Knowledge is how to play a game, intelligence is how to win, wisdom is knowing what game to play.
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 drugs used to effective treat depression, a Reverse Monoamine Oxidase Inhibitor called Manerix is not available for sale in the U.S. because the company that bought the U.S. rights tried to use it to treat dementia, for which it does not work. By the time the trials failed, the patent was too close to running out to run the paperwork for using it to treat depression, for which it does work. Consequently, it is a safe, effective, drug, with nobody in the U.S. to sponsor it to get through the approval process.
SirWired
Shame on you making jokes about this dreadful disease. Alzheimer is a disease which takes a heavy toll on those around the patient. There are some subjects which are better off without jokes involved. This exacerbated need for humour is a symptom of need of being oblivious to a harsh reality. Please, get your act together, folks. Let's show some more respect here.
I used to think that aging was a very complex set of events. Most of the people here do as well, as you can see by reading other peoples comments. I actually still do. but the graph at the end of the explanation page has me at least curious:
http://www.tau-rx.com/quiz/tangles.html
Squarely 100% of the people are at stage 1 by 85. 50% are at stage 3 or higher.
Keeping in mind that: "correlation is not causation", and all appropriate memes for the case:
Do you feel that this could be a fundamental path (albeit not the only necessary one) to tackle aging or its just one in a miriad of problems?
BindO
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!
What a fool believes, he sees, no wise man has the power to reason away.
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.
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.
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.
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.
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 more, and I can't blame her.
This from a guy who used to be very active in the Ham Radio community, a sometimes-tinkerer in programming and circuits, etc. One of the sadder stories, IMO, is of how one time after the onset of the disease (when he could still live at home but had degraded to the point where he couldn't track complicated discussions or follow instructions, etc.) someone from the ham radio community called him up looking to ask him a question - and I guess from the course of the discussion figured out what happened. That must be really sad.
So, yeah, when people post lame jokes like "I was going to post something here but I forgot what" - it's like I want to smack 'em up-side the head and be like, "do you know what this disease really does? It made this man paranoid that my visiting 7-year old cousin might constitute some mortal threat. It's not just about forgetting things."
But, you know what? I also hate this whole attitude of bitching out the "insensitive clods" of the world. Yes, "my dad has Alzheimer's you insensitive clod." But all the same I don't think anything should be considered outside the domain of a good joke. Let's have fun and laugh! :D
Bow-ties are cool.
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....
What happened is that they went to present their results at the ICAD 2008 alzheimer conference in Chicago. The ICAD committee selected Rember as one of the "top presentations" at the conference, and organized all the PR and news briefings.
The "drug" is only a well-known [google.com] synthetic dye [wrongdiagnosis.com]. "Rember" is Methylene blue [thefreedictionary.com]. The Free Dictionary says it is, "A basic aniline dye that forms a deep blue solution when dissolved in water and is used as a bacteriological stain and as an antidote for cyanide poisoning."
"He who toys with the most dyes, wins."
You said, "I should say that Claude Wischik thinks he *does* know what causes Alzheimer's disease. He's sure that tau tangles cause it."
...".
But what causes tau tangles?
Fraud? In my opinion, at the very least the BBC story is very badly written. In my opinion, there are elements of fraud. If I were the manager of "Emma Wilkinson, Health reporter, BBC News" I would review her work to try to discover if she has been taking money to advertise drugs. I would consider firing her, or at least re-assigning her to less demanding writing projects.
Quote from the BBC article: "Rember, or methylthioninium chloride, is the first treatment specifically designed to target the Tau tangles." There was no "design". The effect was discovered entirely because of a laboratory accident with a common laboratory chemical. Quote from the BBC article: "Methylthioninium chloride is more commonly used as a blue dye in laboratory experiments. Professor Wischik discovered it by accident 20 years ago, when a drop in a test tube led to the disappearance of the Tau protein he had been working on."
It seems a bit odd that, if Professor Wischik discovered the effect 20 years ago, there is an investigation of the effect only now. Why the delay? What happened?
Cancer? The BBC article should have mentioned that the laboratory chemical they are now calling "Rember" is an aniline dye, that aniline dyes cause cancer, and that has been known for a long time. Quote from that web page: "A group of chemicals called arylamines are known to cause bladder cancer. These chemicals have been banned in the UK for about 20 years. But it can take up to 25 years for a bladder cancer to develop. You may have been exposed to them a long time ago if you work in industries such as rubber or plastics manufacture. Arylamines that increase risk of bladder cancer include * Aniline dyes
What that quote doesn't say is that direct chemical exposure can cause cancer immediately. How is it possible that "chemicals have been banned in the UK for about 20 years" can be given to people in the U.K. as a drug?
The title of the BBC article is NOT "Alzheimer's drug halts decline". It is "Alzheimer's drug 'halts' decline", but people with no professional writing experience will almost certainly miss the significance of the single quotes, which mean that a claim is merely being made, and the claim is not a verified fact.
The BBC article contains 539 words total. Of those, 243 words, more than half, are quotes. It seems that much of the article may have been taken from a PR release, with little or no critical thinking.
Calling the dye "Rember" encourages those with no scientific training in the field to believe that it will help them "Remember".
There are other odd aspects of the BBC article. The article says, "Trials of the drug, known as Rember, in 321 patients showed an 81% difference in rate of mental decline compared with those not taking the treatment." Does that mean there continues to be mental decline, but the decline is slower?
Later the article says, "Patients with mild to moderate Alzheimer's disease were given either 30, 60 or 100mg of the drug or a placebo. The 60mg dose produced the most pronounced effect - over 50 weeks there was a seven-point difference on a scale used to measure severity of dementia." How many points total are on the scale? Isn't that odd, that the 60 milligram dose worked better than a 100 milligram dose? How much better? Doesn't that say that there were really 3 trials, and one of the dosage levels was by chance statistically better than the others, so it was chosen to report the results?
The BBC article says, "At 19 months there was no significant decline in mental function in patients taking the drug, the researchers said."
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.
Coming soon - pyrogyra
Funny comment. But the underlying facts about the name, and the drug, don't seem funny to me:
1) The person who submitted the story to Slashdot says, The trademark word "rember" is written with a lower-case initial letter. 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, 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".
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.