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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: Twitter: Dereklowe

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August 24, 2010

Alzheimer's: Down With Amyloid?

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Posted by Derek

Here's a fascinating short interview with Mark Smith of Case Western, a leading anti-amyloid-hypothesis guy in the Alzheimer's field. As you'd imagine, he's taking the recent failure of Lilly's gamma-secretase inhibitor in stride.

As you might imagine, he's not shy:

"Everything comes down to how one interprets data. There is a lot of scientific noise out there and most people like to play “follow the leader”. The structure of granting agencies actually discourages anything else. I sense the tide turning but think that the dead horse will be likely flogged for a while yet. For example, the Alzheimer’s field is already moving toward earlier and earlier “diagnosis”. Until these people are subjected to anti-amyloid approaches the field will continue [to support the amyloid theory].

I have received a lot of stick for my scientific talks where for over a decade I have challenged the amyloid hypothesis. I typically tell the audience that my views are controversial and that I would really appreciate someone pointing out a flaw in my logic or presenting evidence that shows that I am wrong. Neither has ever happened."

Comments (6) + TrackBacks (0) | Category: Alzheimer's Disease


1. PharmaHeretic on August 24, 2010 9:15 AM writes...

Kinda like saying, prior to 1930s, that bacteria did not cause infections because nobody had yet developed safe and effective broad-spectrum anti-bacterials.

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2. Cellbio on August 24, 2010 10:11 AM writes...

The quoted section strikes me as the kind of honest language we need in science. Maybe he is not shy, but why should he be? If he is right, then people exposed to certain drugs may see disease exacerbation. Definitely, and sadly, his strong scientific voice and willingness to speak up are often not tolerated in big companies. If all he ever does is criticize, then I would see fault, but if he also offers new paths, then maybe the herd mentality is not only putting people at risk, but failing to advance alternative therapies.

Read the interview, and he apparently predicted worsening of disease with inhibition of gamma-secretase, so a bit more informed opinion about the protective role of amyloid and misguided approaches of today than drawing opinions from failed efficacy.

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3. AlchemX on August 24, 2010 1:10 PM writes...

Do the anti-global warming intervention people have a point also?

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4. john on August 24, 2010 1:45 PM writes...

I think we need to step back and realize that scientific method is about disproving things, no proving things. All theories are scientific because they can be proven false. If, in fact, the amyloid hypothesis is proven false we have moved forward as scientists.
Now if your company has a drug program based on the hypothesis, or your RO1 is mainly synthesizing inhibitors then you've got a problem.
Now is this positive or negative for sufferers of Alzheimers? I don't know, there is progress in that one possible cause may have been eliminated. In the same vein a lot of grant money and R+D money may have been spent while the scientists barked up the wrong tree.
Another question is this, have scientists been claiming to be farther along in understanding the causes of alzheimers than we truly were. Were scientists misleading the public as to how much we understood and how much hope there is for a cure?

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5. ronathan richardson on August 24, 2010 1:54 PM writes...

I'm sort of surprised that much of the debate after this clinical trial ignores everything in the field for the last 10 years. It's become abundantly clear that high-molecular-weight amyloid oligomers are protective, while smaller oligomers of the peptide are extremely toxic. Blocking the accumulation of amyloid can thus increase oligomer lifetime and toxicity. See:

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6. Steven Lin on February 15, 2011 5:14 PM writes...
Sorry to find out that he passed away in an accident.

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