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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline

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August 24, 2012

Lilly's Solanezumab: A Miss or a Win?

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Posted by Derek

Lilly has reported results from its anti-amyloid antibody, solanezumab, and. . .well, it's mixed. And it's either quite good news, or quite bad. You make the call.

The therapy missed its endpoints (both "cognitive and functional", according to the company) in two clinical trials, so that's clearly bad news. Progression of Alzheimer's disease was not slowed. But I'll let the company's press release tell the tale from there:

The EXPEDITION1 study did not meet co-primary cognitive and functional endpoints in the overall mild-to-moderate patient population; however, pre-specified secondary subgroup analyses in patients with mild Alzheimer's disease showed a statistically significant reduction in cognitive decline. Based on those results, Lilly modified the statistical analysis plan (SAP) for EXPEDITION2 prior to database lock to specify a single primary endpoint of cognition in the mild patient population. This revised primary endpoint did not achieve statistical significance.

Now, this news - what you've just read above - actually is sending Lilly's stock up as I write this, which tells you how beaten-down Eli Lilly investors are, or how beaten-down investors in Alzheimer's therapies are. Or both. The headlines are all about how the drug missed in these trials, but that the company sees some hope. But man, is it ever a faint one.

What I'm taking away from the company's statement is that they had a cognition endpoint defined at the beginning of the trial (as well they should). We can assume that it was not a wildly optimistic one; no one is wildly optimistic in this field. And solanezumab missed it in the first Phase III data. But the patients with milder Alzheimer's, when they looked more closely, showed a trend towards efficacy, so they modified the endpoints (that is, lowered the bar and narrowed down to a select population) in the data for the second Phase III before it finished up. And even then, the antibody missed. So what we have are trends, possible trends, but nothing that really gets to the level of statistical significance.

But note, they're talking cognitive efficacy, and there's nothing said about those functional endpoints. If I'm interpreting this right, that means that there was a trend towards efficacy in tests like remembering words and lists of numbers, but not a trend when it came to actually performing better in real-life circumstances. Am I seeing this correctly? Lilly will be presenting more data in October, and we'll know more then. But I'm not getting an optimistic feeling from all this.

I assume that the company is now talking about going back and rounding up a population of the mildest Alzheimer's patients it can find and giving solanezumab another shot. Given Lilly's pipeline and situation, I suppose I'd do the same thing, but this is really a back-to-the-wall move. I think that you'd want to see something in a functional endpoint to really make a case for the drug, for one thing, and out in the real world, diagnosing Alzheimer's that early is not so easy, as far as I know. Good luck to them, but they are really going to need it.

Comments (59) + TrackBacks (0) | Category: Alzheimer's Disease | Clinical Trials


COMMENTS

1. anon2 on August 24, 2012 11:05 AM writes...

Afraid that this will be throwing good, fresh funds after that which has already been spent in disappointing results.

And why is it, again, that extra funds used in stock buybacks should instead be applied to R&D?

Permalink to Comment

2. ScientistSailor on August 24, 2012 12:12 PM writes...

Actually, this makes sense, IF you believe the window hypothesis for Abeta. The earlier you treat, the better. Genentech is trying their anti-Abeta antibody in a prophylactic study, treating subjects years before they have symptoms. To go back to the thread on GNE vs. Roche, think Roche would ever try something like that??

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3. NoDrugsNoJobs on August 24, 2012 1:20 PM writes...

#2 - Spot on. The race is presently on for picking the best abeta therapys for treating very, very early stage. To me, this is the only thing that could have been expected to make sense. I would find it hard to fathom an anti-AB therapeutic that would reverse brain damage. I don't know of any drug that reverses brain damage but if you are talking about reducing the formation of the brain damage causative agent, well now I think you are talking. Damn it though, I am afraid it will be too late for me already!

Permalink to Comment

4. Hap on August 24, 2012 1:50 PM writes...

1: Because no R+D = no drugs. If you think that R+D = no drugs, then you should be shipping all of your money back to investors because you have no business - buying back the stock is like making sure the Titanic's sponge mops are dry and ready for use.

If management can't find anything useful to do with their money, perhaps they should leave it to someone more competent, or at least someone less expensive. That's been their philosophy in other areas - considering their performance, it can hardly work worse.

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5. Howie on August 24, 2012 2:59 PM writes...

@ Derek and anon2: I don't think that looking early onset patients is a "back to the wall" move. Nor is it throwing good money after bad. This is a new hypothesis, and a logical one at that. How can pharma be expected to make any advances for new and difficult therapies without taking well-reasoned risks? It takes courage to see a hypothesis through, and I for one admire Lilly's commitment to AD patients.

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6. pokey on August 24, 2012 3:45 PM writes...

FDA Approves Amyvid™ (Florbetapir F 18 Injection) for Use in Patients Being Evaluated for Alzheimer's Disease and Other Causes of Cognitive Decline

This it Lilly's compound. Maybe there is a plan in there somewhere. Seems to me this technique would be very helpful in diagnosing early stages of plaque formation would it not?

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7. needabetaguess on August 24, 2012 7:19 PM writes...

Spin, pure and simple. Better to keep the lifeboats on deck than to have everyone abandon ship.

Look at the CNS turnover rate for Abeta. It's doing something important and likely unmanageable using a biochemical sponge approach.

I'd never let a friend or relative take an Abeta antibody.

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8. Colonel Boris on August 24, 2012 7:25 PM writes...

If it works as a successful preventative, then it will make far more money for them than an actual cure. If it had been a cure, then it would probably be used once or twice on each patient until they were cured - decent sales there. If it's a preventative, then many more people would take it for the rest of their lives just in case - much bigger volumes there.

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9. Lane Simonian on August 24, 2012 9:12 PM writes...

Amyloid plaques are only an intermediate step in the formation of the ultimate culprit in Alzheimer's disease: peroxynitrites. The two are interconnected: the same basic pathway (phospholipase C activation) leads to both, amyloid plaques increase the formation of peroxynitrites, and peroxynitrites in turn increase the aggregation of amyloid plaques. Phospholipase C gamma inhibitors (such as phenols in various herbs, spices, and essential oils)partially inhibit the formation of both amyloid plaques and peroxynitrites and thus likely delay Alzheimer's disease. Here is the critical point, even if you could remove all of the plaques, the damage done by peroxynitrites would remain. Methylphenols compounds in various essential oils and herbs inhibit the formation of peroxynitrites, scavenge peroxynitrites and reverse part of the oxidative and nitration damage that they do to receptors, proteins, and enzymes critical for short-term memory, mood, sleep, alertness, awareness, social recogntion, neuronal survival, and neuronal regeneration. Peroxynitrite scavengers have time and again ameliorated Alzheimer's disease in mice and human clinical trials. If researchers and pharmaceutical companies would drop their blinders the path to treating this disease is clear. It can be treated effectively, cheapily, and in most cases with few side effects with the methylphenols compounds found in various herbs and essential oils.

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10. Idiotraptor on August 25, 2012 6:38 AM writes...

@9:

I'm so glad to learn the solution to treating AD is immediately available.

Please document and cite references for the human and murine studies which demonstrate effective activity of peroxynitrite scavengers.

Permalink to Comment

11. Anonymous on August 25, 2012 7:16 AM writes...

@9

Are these scavengers found in snake oil by any chance??

Permalink to Comment

12. Lane Simonian on August 25, 2012 10:15 AM writes...

I would be pleased to cite the studies where peroxynitrite scavengers have effectively ameliorated Alzheimer's diseae in mice or human beings. I will post those separately so they don't get lost in this message. I wanted to point out that every currently prescribed medication for Alzheimer's disease contain methyl groups. Methyl compounds bind to peroxynitrites but at the levels found in the drugs they do not inhibit peroxynitrite formation. They thus only temporarily slow down the disease. Phenol groups are excellent antioxidants in part because they inhibit most of the enzymes that lead to the formation of peroxynitrites (phospholipase C gamma, NADPH oxidase, and IkB kinase/Nuclear Factor k B). Phenols are excellent hydrogen donors so they convert peroxynitrites into water and a nitrogen dioxide anion (ONOO-=H20 + NO2-). The problem with phenols is several fold: they can activate a fourth enzyme involved in the formation of peroxynitrites--phospholipase C beta, they can act as prooxidants at too low or two high of levels, they may be metabolized, absorped, or excreted before they reach the brain in large enough concentrations. On the other hand, the methoxyphenols (primarily eugenol, carvacrol, and thymol) in various essential oils are highly concentrated and directly reach the part of the brain most affected by Alzheimer's disease--the hippocampus. They are thus highly suited to treat the disease.

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13. DrSnowboard on August 25, 2012 10:56 AM writes...

"Methyl compounds bind to peroxynitrites but at the levels found in the drugs they do not inhibit peroxynitrite formation"

Pseudoscience bullshit. Please go back and rewrite your nutraceutical marketing to not include total bollocks. Thank you.

Permalink to Comment

14. Anonymous on August 25, 2012 11:35 AM writes...

I hope that I am not at this all day. Almost everything I say is backed by research.

I have just posted (or tried to post) about a dozen studies in which peroxynitrite scavengers have ameliorated Alzheimer's disease in human beings or animals. I am not sure what this site's policy is on links, so let me just point you to the primary author and title for the human clinical trials.

Jimbo, Effect of aromatherapy on patients with Alzheimer's disease.

Akhondzadeh following three studies

Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomized and placebo-controlled trial.

Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial.

Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16-week, randomized and placebo-controlled trial.

Goswami, Effects of Bacopa monnieri on Cognitive functions in Alzheimer's disease patients.

For evidence that methyl groups (CH3) bind to peroxynitrites go to google images and type in peroxynitrous acid.

For evidence that the methyl compounds in currently prescribed medications don't inhibit peroxynitrite formation see Hwang, et al. Microglia signaling as a target of donepezil (Aricept).

People tend to forget that plants and plant extracts contain chemicals as well and that in proper concentrations these chemical are much better at treating the disease than the medications currently prescribed for the disease.

I don't mind the critics but at least look at the research before reaching such strong-minded conclusions.

Permalink to Comment

15. DrSnowboard on August 25, 2012 12:54 PM writes...

If you are going to try to use scientific terms, please be accurate. Google images 'peroxynitrous acid' gives no image that would support your claim that 'methyl groups bind to peroxynitrites' . Or methoxy groups. Please prove me wrong by describing that image.

I would prefer that everything you say is backed by research. True you provide partial references to small (n=42) , short (16weeks) studies that are RCT's. The last reference was uncontrolled.

Let the AD experts discuss your claims further.

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16. John Wayne on August 25, 2012 1:08 PM writes...

"I wanted to point out that every currently prescribed medication for Alzheimer's disease contain methyl groups. Methyl compounds bind to peroxynitrites but at the levels found in the drugs they do not inhibit peroxynitrite formation."

Looks like Lane Simonian found the 'magic methyl' we have all been hearing about.

Lane, it is extremely hard to take you seriously when you say things that cannot possibly be true; I will give two examples. In the above quote, you say that methyl's bind to peroxynitrites. Not only is this a very odd statement, even if it was true it could not be true for all versions of the methyl group.

Permalink to Comment

17. Lane Simonian on August 25, 2012 2:34 PM writes...

The google image of a methyl group (CH3) binding to peroxynitrite (ONOO-) from google is
O=N-O-0-CH3. The following article supports the claim that methyls bind to peroxynitrites:

EDTA bis-(methyl tyrosinate): a chelating peptoid peroxynitrite scavenger.
Fisher AE, Naughton DP.

The magical "methyl" is a good turn of phrase but it really is the magic methylphenol (or methoxyphenol in the case of eugenol). Here is evidence that eugenol, carvacrol, and thymol found in various essential oils can be used to treat Alzheimer's disease.

Effects of Eugenol on the Central Nervous System: Its Possible Application to Treatment of Alzheimer's Disease, Depression, and Parkinson's Disease
Author: Irie, Yoshifumi
Source: Current Bioactive Compounds, Volume 2, Number 1, March 2006 , pp. 57-66(10


Behav Pharmacol. 2012 Jun;23(3):241-9. doi: 10.1097/FBP.0b013e3283534301.
Cognitive-enhancing activity of thymol and carvacrol in two rat models of dementia.
Azizi Z, Ebrahimi S, Saadatfar E, Kamalinejad M, Majlessi N.
SourceDepartment of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran.

And that essential oils via aromatherapy have ameliorated Alzheimer's disease in mice.

Inhaled essential oil from Chamaecyparis obtuse ameliorates the impairments of cognitive function induced by injection of β-amyloid in rats.

Pharm Biol. 2012 Apr 3;

Authors: Bae D, Seol H, Yoon HG, Na JR, Oh K, Choi CY, Lee DW, Jun W, Lee KY, Lee J, Hwang K, Lee YH, Kim S

Am J Chin Med. 2011;39(5):917-32. doi: 10.1142/S0192415X11009305.
SuHeXiang Wan essential oil alleviates amyloid beta induced memory impairment through inhibition of tau protein phosphorylation in mice.
Jeon S, Hur J, Jeong HJ, Koo BS, Pak SC.
SourceDongguk University Research Institute of Biotechnology, Seoul 100-715, Republic of Korea. jsong0304@dongguk.edu

And one last one for rosmarinic acid.

Behav Brain Res. 2007 Jun 18;180(2):139-45. Epub 2007 Mar 12.
A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Abeta(25-35).
Alkam T, Nitta A, Mizoguchi H, Itoh A, Nabeshima T.
SourceDepartment of Neuropsychopharmacology & Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.

The evidence is there. One can reject it out of hand if one wishes. Or one can constructively criticize the studies (which is good). But it is very hard to deny that peroxynitrite scavengers partially reverse Alzheimer's disease.


Permalink to Comment

18. DrSnowboard on August 25, 2012 2:48 PM writes...

Oh, making the methyl ester of peroxynitrous acid magically shows methyl groups 'bind' to peroxynitrous acid?
You , sir / madam, are a troll.
Sadly the comments of In The Pipeline tend to be inhabited by the chemistry community who will gently giggle at your chemistry 101 fail bullshit arguments so repeated pasting of your lit refs is unlikely to infomercial them.

Please try harder.

Permalink to Comment

19. Anonymous on August 25, 2012 2:49 PM writes...

@Lane,

It is a moot point whether methyl groups scavenge peroxynitrite and the relationship of this to ALzheimer's, since there is not one single successful therapy for Alzheimer's.

Indeed, even if you were correct re: methyl groups and peroxynitrites, the data you present would argue that peroxynitrites had no important role to play in Alzheimer's, since scavenging them had no impact on the disease.

Permalink to Comment

20. Anonymous on August 25, 2012 2:50 PM writes...

@Lane,

It is a moot point whether methyl groups scavenge peroxynitrite and the relationship of this to ALzheimer's, since there is not one single successful therapy for Alzheimer's.

Indeed, even if you were correct re: methyl groups and peroxynitrites, the data you present would argue that peroxynitrites had no important role to play in Alzheimer's, since scavenging them had no impact on the disease.

Permalink to Comment

21. Lane Simonian on August 25, 2012 3:58 PM writes...

That peroxynitrite-mediated damage is widespread in Alzheimer's disease has been known since the mid-1990s.

Widespread Peroxynitrite-Mediated Damage in Alzheimer’s Disease
Mark A. Smith1, Peggy L. Richey Harris1, Lawrence M. Sayre2, Joseph S. Beckman3, and George Perry1

Am J Pathol. 1996 July; 149(1): 21–28. PMCID: PMC1865248
Evidence of neuronal oxidative damage in Alzheimer's disease.
P. F. Good, P. Werner, A. Hsu, C. W. Olanow, and D. P. Perl

Would it not make sense if peroxynitrite-mediated damage is widespread in Alzheimer's disease that compounds which inhibit the formation of peroxynitrites, scavenge peroxynitrites, and repair part of the oxidative and nitration damage caused by peroxynitrites would be useful in treating the disease? Compounds containing methyl and/or phenol groups scavenge peroxynitrites. Of the two, though, only phenols strongly inhibit the formation of peroxynitrites and that largely explains why compounds containing methyphenols (or methoxyphenols) treat the disease better than methyl compounds alone.
The following article supports this cotention.

J Pharm Pharmacol. 2002 Oct;54(10):1385-92.
Selective peroxynitrite scavenging activity of 3-methyl-1,2-cyclopentanedione from coffee extract.
Kim AR, Zou Y, Kim HS, Choi JS, Chang GY, Kim YJ, Chung HY.
SourceCollege of Pharmacy, Pusan National University, Busan 609-735, Korea

Furthermore, MCP only weakly suppressed NO production, which is one of the upstream sources of ONOO- in-vivo, suggesting that NO production may be not a pharmacological target for MCP. Taken together, our results suggest that MCP may be regarded as a selective regulator of ONOO- -mediated diseases via direct scavenging activity of ONOO-.

[this article suggests that electron transfer is the mode of peroxynitrite scavenging by methyl compounds; it does not matter to me what the mechanism or mechanisms are just as long as it is established that compounds containing methyls are peroxynitrite scavengers].

The compounds that have shown effectiveness in human clinical trials have primarily involved methylphenols and methoxyphenols which suggests that these combined compounds are more effective at treating Alzheimer's disease than either methyl or phenol compounds alone.

I am not sure where the problem with citing references is coming from unless it is upsetting someone's ingrained beliefs about the causes and treatments of Alzheimer's disease. If study after study after study with peroxynitrite scavengers produces the same positive results, then at some point even the most hardened and flippant skeptics, have to begin to reconsider. Focus on the right target and you will get the right results.

Permalink to Comment

22. DrSnowboard on August 25, 2012 5:13 PM writes...

I am not flippant about your claims. I am angry. You sloppily use chemical terms , present some information as proven fact, some elisions and simplifications to aid your claims. If you have the evidence in your literature regurgitation, which I doubt, you present neither a coherent argument or a tone which suggests a scientific basis.
I'm out.

Permalink to Comment

23. Lane Simonian on August 25, 2012 6:02 PM writes...

I have presented five clinical trials in which peroxynitrite scavengers improved cognitive function and/or personal orientation in people with Alzheimer's disease (albeit of limited size and duration and one did not have a control group). I have presented a few animals trials (and I could have provided a dozen more) in which peroxynitrite scavengers have ameliorated Alzheimer's disease in mice. So I don't understand why you are angry or why you were having troubles following my argument. Let me make it as simple as possible.

Peroxynitrites are dircetly or indirectly responsible for every aspect of Alzheimer's disease.

Peroxynitrite scavengers partially reverse Alzheimer's disease in animals and human beings.

Not too complicated is it. Most diseases are easy to treat once you identify the causal agent. The causal agent is not amyloid plaques (which are an intermediate step in Alzheimer's disease) and not neurofibrillary tangles which are caused by peroxynitrites, the problem is peroxynitrites. That's why every effort to treat this disease by somehow removing plaques or reversing the hyperphosphorylation of tau proteins will fail from now until eternity. At the very best they will stop the progression of the disease, they will never partially reverse it.

Peace out.

Permalink to Comment

24. Anonymous on August 26, 2012 3:58 PM writes...

Lane

Please have a look at the structures of human amino acids (basic biochemistry text boook). See how many have methyl groups. If this was the simple answer to AD the disease would never exist as the human body would just soak up the peroxynitirtes naturally.

If your answer was correct, then Wal-Mart would be making a fortune selling these oils. They are not - it is not a conspiracy (Pharma blinkers or not). These papers are just crap - just because they have been published does not make a difference. Animal trials are total crap - mice do not get AD (this goes for Pharma LMW drugs also).

We do not understand much about AD. This is why BS can exist for a time in this area but I am sure over time science will win out and we will understand what is really causing it and how to treat it but until then please don't give false hope to patients who think your pseudoscience will save them - it will not.

Peace

Permalink to Comment

25. Jose on August 26, 2012 7:19 PM writes...

OK, perhaps it's time to stop feeding the (pseudoscientific babble-bot google scholar-regurgitating) troll.

Permalink to Comment

26. Lane Simonian on August 26, 2012 8:20 PM writes...

A few corrections from previous posts the ONOO-CH3 image should have been labelled methyl peroxynitrite. Again, it does not matter to me if methyl groups bind to peroxynitrites or reduce them, just as long as they scavenge them.

A more important point is that several people seem to be missing the argument. Methyl groups scavenge peroxynitrites but they do not inhibit their production. See study on coffee extract above. So if the production of peroxynitrites reaches a certain level, the ability of the body to detoxify them whether by endogenous or exogenous antioxidants is not going to make a difference unless their production can be stopped or sharply curbed. Indeed that is part of the problem with Alzheimer's disease, the main internal antioxidant (glutathione) that detoxify peroxynitrites are depleted by peroxynitrites. The problem with the drugs currently being used to treat the disease is that they are simply not very effective antioxidants, in part because they do not stop the formation of peroxynitrites.

Focus more on the phenols than on the methyls (in regards to the methyls all I am saying is that two peroxynitrite scavengers are better than one). Phenols inhibit phospholipase C gamma which is linked both to the formation of amyloid plaques and to peroxynitrites. It may activate phospholipase C beta which triggers the same pathway as phospholipase C gamma (protein kinase C, release of intracellular calcium, the production of superoxide anions via NADPH oxidase, and the production of inducible nitric oxide via IkB kinase/Nuclear Factor kappa B) that lead to the production of peroxynitrites. But phenols inhibit both the production of superoxide anions and inducible nitric oxide limiting the formation of peroxynitrites.

Moreover, phenolic compounds can partially reverse the oxidative damage done by peroxynitrites and may be able to de-nitrate proteins. Phenols thus act in a threefold manner: they limit the formation of peroxynitrites, intercept peroxynitrites, and repair part of their damage.

Toxicol Lett. 2003 Apr 11;140-141:125-32.
Defenses against peroxynitrite: selenocompounds and flavonoids.
Klotz LO, Sies H.
SourceInstitut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Postfach 101007, D-40001, Düsseldorf, Germany.

Abstract
The inflammatory mediator peroxynitrite, when generated in excess, may damage cells by oxidizing and nitrating cellular components. Defense against this reactive species may be at the level of prevention of the formation of peroxynitrite, at the level of interception, or at the level of repair of damage caused by peroxynitrite.

It does not help me or anyone else to say that the studies are full of crap. I agree that the value of mice studies is quite limited. Granted the human clinical trials were small and of a limited time frame but as far as I know there are no other clinical trials in which cognitive function has improved with any other type of treatment. And if you look at the studies they were all with compounds containing methylphenols or methoxyphenols (rosemary essential oil, lemon balm essential oil, sage essential oil, Bacopa monnieri, and saffron). This may just be a coincidence but I doubt it.

This is not psudoscience--the compounds in essential oils are real. The compounds in essential oils containing methyl but not phenol groups are not effective at improving cognitive function (on the other hand, many of them act as sedatives whereas the more stimulating essential oil containing phenols can increase anxiety, high blood pressure, and seizures in Alzheimer's patients with high levels of adrenaline which is an important subset of the Alzheimer's population).

A number of scientists are trying to develop a polyphenolic spray to treat Alzheimer's disease. But why reinvent the wheel when you can already deliver phenolic compounds directly to the hippocampus via aromatherapy. There is little to no chance of the methylphenols to be excreted, metabolized, or absorped. Not only that the methylphenols or methoxyphenols in various essential oils are highly concentrated. And in general with the exceptions noted above inhaling methylphenols is safer than ingesting them (even when diluted) because the latter route can damage the liver and kidneys.

Please read the studies again carefully. Unless, the scientists doing them were falsifying the data or completely botched them it is hard to explain the results in any other way than there were improvements in cognitive function and/or personal orientation.

I don't mind criticism but it should be based on some foundation rather than just tossing out epithets and making misleading inferences. Just not liking the answer is not the same thing as refuting the answer. The latter requires a great deal of more effort, if possible at all.

Permalink to Comment

27. Lane Simonian on August 26, 2012 8:48 PM writes...

Yes unless you have something constructive to say stop feeding me. I have had scientists engage me on a very constructive level, adding where they agree and disagree with this hypothesis. I am not interested in sparring with people or trading insults. I am interested in understanding this disease and effectively treating it, and eight years and hundreds of hours of research has gotten me to the doorstep.

Permalink to Comment

28. lightworkweek on August 26, 2012 10:07 PM writes...

"Hundreds" of hours in eight years? I've spent more time making coffee. A simple Google search shows you've likely spent more time blogging about AD than actually studying it. I'd say get back to the bench, but The Google tells me that might be a waste of calories.

Permalink to Comment

29. Lane Simonian on August 26, 2012 11:26 PM writes...

I spend more time blogging about Alzheimer's disease than researching it these days because the research is at the point of diminishing returns and it is a more effective use of my time to make people aware of the research (although apparently not on this site).

I see people don't like google searches, but what is printed on google scholar is the original research articles. There is no advantage to me to going to the medical school library and printing off the journal aritcles from there.

So I wonder where is all the antipathy coming from. Do you believe that diseases can only be treated with pharmaceutical drugs? Do you think the scientists producing these studies in foreign countries did not receive a proper medical education in which they were taught that botanical and nutraceutical approaches to diseases were pure garbage? Do you think that they were just extraordinarily poor researchers who unfortunately did not have the good fortune of a U.S. medical education? Were they clearly incapable of running simple diagnostic tests for cognitive function or had no idea how to run double-blind placebo controlled studies? The fact that almost all of these studies were undertaken outside of the United States reflects an underlying bias in much of U.S. medicine (and I won't say Western medicine because some of these studies were undertaken in places like Great Brtain and Italy) that is troublesome. And some of the comments made on this site reflect a fundamental lack of interest in a hypothesis that while not in the mainstream was initiated by some of the pioneers in the field. If you have a personal interest in trying to refute this hypothesis that should be stated upfront. But if you are interested in refuting this hypothesis for whatever reason please do a much better job; otherwise it does indeed waste everyone's time. You may be professionals but your responses show a deep lack of professionalism.

Go back and read the studies once more. If since the 1990s, it was known that peroxynitrite-mediated damage was widespread in Alzheimer's disease and every peroxynitrite scavenger tested has helped ameliorate the disease in either mice or human beings--tell me constructively (and I am begging you this time) where the error lies.

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30. lightworkweek on August 27, 2012 8:25 AM writes...

Lane, your treatise looks like a gibberish-flavored word salad, but it's in many ways more logical that the idiotic peripheral sink hypothesis that drove solanezumab forward. At least aromatherapy can make the room smell good, and it certainly doesn't amount to elder abuse like certain recently failed Abeta antibody drugs.

From your posts on the NIH website, it seems likely that you're too close to the disease to proffer sound hypotheses. Maybe you should take a breather for a couple of years, then reassess where you should focus your efforts? IMO, Pharma should be doing the same in the Alzheimers arena.

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31. MTK on August 27, 2012 9:06 AM writes...

Lane,

Serious question.

If Alzheimer's can be treated so cheaply and effectively and has the proper scientific basis as you suggest, why don't you start your own company and prove it through clinical trials?

I'm not kidding or being snarky, either. Plenty of companies have been started with less. You shouldn't have any trouble getting investors either for a market this big with an approach that promising.

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32. Anonymous on August 27, 2012 9:10 AM writes...

Lilly's press release emphasizes that when they pooled the data from both studies, then they saw statistically significant slowing of cognitive decline in the overall study population and in the subset of patients with mild disease. This may be because they are increasing their sample size when they pool the data from 2 studies. I'd be curious to know whether the magnititude of the slowing of cognitive decline is clinically meaningful. The press release does not address this.

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33. Lane Simonian on August 27, 2012 10:05 AM writes...

I can finally work off of something that is meant to be positive. Yes, attempts to remove plaques is a dangerous strategy. At the very best it will only stop the progression of the disease. It will not repair the damage that has already been done.

Funny if you mix the wrong oils together, you can make a room smell really bad for days. I bought the line for years that aromatherapy produced no side effects. But the oils which most improve cognition can significantly increase agitation in some people (and the reverse is also true the oils that reduce agitation do not have much impact on cognition, so maybe they need to used in conjunction with each other). Allergic reactions, seizures, and an increase in high blood pressure are additional concerns. But for most Alzheimer's patients,aromatherapy is not only more effective it is much safer than prescribed drugs for the disease.

I have not cited institutional case studies up to this point, as these are not considered scientific by scientists, but I believe they have some value.

Int J Nurs Pract. 1998 Jun;4(2):70-83.
New approaches to health and well-being for dementia day-care clients, family carers and day-care staff.
Kilstoff K, Chenoweth L.
SourceFaculty of Nursing, University of Technology, Sydney, Australia. Kathy.K