Sunday, April 6, 2008

20 Years of Wasted Research? Beta-Amyloid Theory Called into Question, Again.

Science Daily reports that University California, Irvine reports that a promising Alzheimer’s Vaccine tested in a canine succeeded in clearing beta-amyloid plaques but failed to demonstrate ecologically results of restoring memory and/or learning ability. This is no surprise.

The near religious zealotry that has surrounded beat-amyloid theory has caused the loss of many promising avenues of research over the last 20 years. If the Elan/Wyeth AD Vaccine in phase III trials demonstrates plaque reduction without ecological validity, it should not be marketed. Beta-amyloid is a surrogate marker for Alzheimer’s not the outcome (Most 50 year-olds have some plaques and tangles without exhibiting AD). Further, any drug seeking to FDA approval must demonstrate a direct benefit of increased ir stable memory and learning capacity relative to the expected decline in the disease. (In no way does the editor supports the use of the ADAS-Cog endpoint, it is flawed and borders on useless.) Also, it would be useful to measure the effect on psychiatric disorders presented by many dementia patients.

We will shortly see the results of several late-stage clinical trials that have targeted beta-amyloid, and I am not sanguine. Dementia is very complicated and Alzheimer’s disease is a subset of the space. Many patients with Alzheimer’s have other forms of dementia. Measurement is very challenging. Any approval of an agent should not rely on anything other than the patients’ cognitive performance and mental condition. The failures in dementia research are so myriad that it defies description.

In the event beta-amyloid therapies fail in humans, it is time to replace the entire leadership of Alzheimer’s research across the board from universities, foundations, not-for-profit organizations, pharmaceutical companies and government agencies. (Pharma has already starting moving its chips as its researchers are only vested in producing drugs that can be marketed.) They bet big on one theory resulting in the dismissal of alternative theories and insured that we will be set back 20 years. Not only was this ill-informed, it demonstrated an arrogance that is unsuitable in science. A younger generation of researchers have a vastly better understanding of the disease and maintain open minds. Much as Dr. Anthony Fauci has recently called for new generation to take up the mantle of developing an AIDs vaccine, it is time dementia research follow suit. The old guard is invested in proving its theory was correct so they can keep getting grants. Admit the failure and get on to solving the problem.


a.crosbie said...

Why do you suggest that the new drug should demonstrate results of "restoring memory and/or learning ability" to be a valid approvable product?

If the efficacy is in the area of delaying deterioration, is this not a beneficial thing?

This is a question without bias, I'd liker to understand what you mean...

Editor said...

You are quite right and the post has been edited to reflect your comment.

Any drug demonstrating a stable patient response or the mitigation of expected decline in memory and or learning certainly warrants approval if the agent achieves statistical significance.

Wyeth has applied a diverse range of approaches, and we would expect a cocktail of compounds to be applied over the course of the disease.

Good luck.

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