Corante

About this Author
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

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« Vaccines by the Dozen | Main | A Smelly Riddle »

April 14, 2005

How Good Is Aricept, Anyway?

Email This Entry

Posted by Derek

Pfizer and Eisai picked up some headlines on the news that their Alzheimer's drug, Aricept (donezipil) showed some effectiveness in delaying the onset of Alzheimer's. That used to be my field of work, although I've got no competing interest in that therapeutic area now. I make that disclaimer up front, because I'm not all that impressed by this new study.

Aricept is a cholinesterase inhibitor, part of the first wave of compounds that were brought in as Alzheimer's therapies. Inhibiting cholinesterase increases the amount of a key neurotransmitter (acetylcholine) that hangs around in the synapse, which should, in theory, lead to stronger signaling between neurons. But this is and always has been a brute-force mechanism, real back-of-the-envelope stuff, which I realized even when I used to work on something pretty similar.

We don't understand neurotransmission well enough to be sure that we're doing much good just by turning up synaptic signaling. To add to the problem, the relevant cholinergic neurons are among those being damaged by Alzheimer's itself, so the drug's therapeutic target is slowly disappearing. That's why the cholinesterase inhibitors are recommended for very early stages of Alzheimer's, and are considered useless for late stages of the disease.

And that's why Pfizer went out as early as possible, out to before patients had even shown signs of Alzheimer's at all. It appears that Aricept therapy helped slow the onset of the disease, among those who developed it at all. Problem is, the effect wasn't large, and after three years any benefit had completely disappeared. The placebo-treated Alzheimer's patients were in the same shape as the ones who had been getting Aricept all along. (Note that Aricept has been studied in non-Alzheimer populations before.)

You wouldn't know all this from a quick look at most of the popular press, though, which went with New Breakthrough headlines like "Drug is First to Delay Onslaught of Alzheimer's." (Science, on the other hand, went with "Study Questions Efficacy of Popular Alzheimer's Treatments", which is more like it.) I'm in the same camp, and it's the same one as the editorial from the issue of the New England Journal of Medicine where the study appeared. Aricept, the journal said, "may offer some benefit, but any such benefit is quite limited and apparently transient" Try turning that into something that'll make you sit past the commercial break. . .

Comments (8) + TrackBacks (0) | Category: Alzheimer's Disease


COMMENTS

1. Eric Garland on April 15, 2005 9:06 AM writes...

I guess the question is, do amyloid plaques cause Alzheimer's, or does Alzheimer's cause amyloid plaques? And is that really the question at all?

I have studied the acetylcholinesterase inhibitor class before, but I had no idea that there was so little effect from the "gold standard."

I think the issue here is how good Pfizer's marketing is. Families members feel completely helpless, and if a drug can make them feel like at lease they are delaying the inevitable, the benefit may be perceived as strong.

Besides, aren't there studies that show AChEIs keep people out of nursing homes longer?

Permalink to Comment

2. Jason on April 15, 2005 9:48 AM writes...

So Aricept is like Sarin, only gentler.

Permalink to Comment

3. Derek Lowe on April 15, 2005 10:17 AM writes...

That's mechanistically true, but it's true for all the cholinesterase inhibitors. There's a range of activities.

Some years ago, Bayer was developing a compound called metrifonate, which was more of an irreversible inhibitor (as opposed to Aricept, which is slow-reversible.) The compound dropped out of advanced clinical trials due to cholinergic side effects in a few susceptible patients.

Permalink to Comment

4. Kevin on April 15, 2005 6:18 PM writes...

what about the glutamate pathway drug Namenda?


Permalink to Comment

5. KDH on April 15, 2005 9:16 PM writes...

Very weak molecule with an overzealous sales and marketing team. The company is unethical and should be investigated by FDA for their dangerous and misguided promotion of Namenda!

Permalink to Comment

6. Richard on April 16, 2005 8:37 PM writes...

Any comment on Myriad Genetics's alzheimer's drug Flurizan? Now in Phase III testing, (while still awaiting Phase II results!) A bit like Ibuprofen, as I understand it.

Permalink to Comment

7. PacRim Jim on April 16, 2005 9:44 PM writes...

Pharma development seems quite primitive. I imagine trying to repair a broken computer motherboard by increasing or decreasing any particular component, but it makes no sense. Until systemic remedies become available, our treatments cannot be wholly effective, or so it seems to me.

Permalink to Comment

8. Zack Lynch on April 20, 2005 1:00 PM writes...

Derek, Keep writing about neuropharma!!!

I moderated a panel last night at Stanford with a couple of interesting companies that are working on AD treatments. Ceregene, in particular, seems promising....

Permalink to Comment


EMAIL THIS ENTRY TO A FRIEND

Email this entry to:

Your email address:

Message (optional):




RELATED ENTRIES
XKCD on Protein Folding
The 2014 Chemistry Nobel: Beating the Diffraction Limit
German Pharma, Or What's Left of It
Sunesis Fails with Vosaroxin
A New Way to Estimate a Compound's Chances?
Meinwald Honored
Molecular Biology Turns Into Chemistry
Speaking at Northeastern