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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.)"
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 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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man: no entry for woman in the manual.
"Qua!?"
I saw a talk by Peter St George Hyslop on this subject a couple of weeks ago. The current thinking is that the presence of smaller beta amyloid oligomers lead to the formation pathogenic form of tau. Whether it's the tau or the beta-amyloid itself that leads to the cognitive impairment is still debated, while this work suggests that the tau is most important, one of my students is presenting work at the same meeting that suggests soluble beta amyloid concentrations (rather than plaques) are key. Neither conclusion to my mind is completely satisfactory.
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....
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.