Anavex Life Sciences Corp (AVXL)

[F1ash]

Dr.George Perry....can someone explain his relationship with Anavex ? I realize he is not an employee or on the SAB and I see him quoted in PR's from the company...

He is a highly cited source and was likely asked to comment by Anavex. He likely just obliged Anavex’s request for comment.

“According to our Special Topics analysis on Alzheimer's Disease, the work of Dr. George Perry ranks at #2 by total papers and #7 by total cites, based on 292 papers cited a total of 11,180 times during the analysis period. Two of these papers appear on the top 20 papers lists.”

And he seems to believe the focus of Alzheimer’s treatment needs to shift from only Plaque removal to a broader approach that could perhaps include A2-73.



“SW: So you don't think amyloid accumulation triggers the disease process as Dennis Selkoe suggests?

His view and ours are diametrically opposite.

SW: OK, tell us yours.

Ours is that amyloid is a response to the disease, not the cause of the disease. Amyloid is not irrelevant. It's very, very important. So I don't differ from Dennis in that sense, because we both believe amyloid is important.

Why? There are several reasons. One is vaccines. When amyloid is removed from brains using vaccines, it doesn't help patients. In fact, patients got slightly worse. This is true in all the studies. Further, when one sees amyloid deposition in the brain, oxidative damage decreases. So there's an inverse correlation. Whether oligomers or fibers, when we see amyloid increased, we see a decrease in the levels of oxidative damage. One important mechanism for amyloid's apparent antioxidant activity is that it binds copper and redox silences it.

With my colleague Mark A. Smith, also a highly cited person who unfortunately died in December, we've written probably about 100 publications questioning the amyloid-cascade hypothesis.

"If I had to make one guess at this point, I'd say Alzheimer's disease is a metabolic disease."

The amyloid cascade hypothesis is a very simplistic view that was useful to consolidate many observations under testable hypotheses. Failure of those tests has now put the hypothesis in question. Unfortunately the cascade hypothesis is fundamentally an abiological concept. It goes against evolutionary selection; it does so by proposing a well-adjusted organism would produce a response that has but a detrimental effect. For a response to develop in the body it must have some adaptive value.

SW: So you're presuming it's a response to oxidative stress?

Exactly. I'm proposing amyloid is an adaptive response, based on some of what we already discussed.

SW: That oxidative stress goes down when amyloid accumulation goes up?

That's one—oxidative stress goes down when amyloid goes up, and when we remove amyloid people actually get worse. Again, I'm not proposing the amyloid is irrelevant. And we're not the only ones who question the amyloid cascade hypothesis. Many people do. Most say it's secondary. Some say it's irrelevant. I think it's a critical part of the disease process, but not the trigger.

SW: So your hypothesis would be that oxidative stress triggers the disease process?

Not exactly. Our hypothesis is that oxidative stress is a window for looking at the disease, just as amyloid is also a window. People elicit a number of responses as Alzheimer's develops. The key thing to determine is where the oxidative stress originates. There has to be an abnormality that predates oxidative damage. Amyloid is not the primary abnormality because amyloid, if anything, reduces oxidative stress.”

http://archive.sciencewatch.com/ana/st/alz2/11monSTAlz2Perr/