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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'? :?
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.
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.
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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
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.
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".
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.
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.
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 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.