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.

Reversal Of Alzheimer's Symptoms Within Minutes In Human Study

The ScienceDaily reported on January 9th an extraordinary new scientific study, which for the first time documents marked improvement in Alzheimer’s disease within minutes of administration of a therapeutic molecule. The article referenced has been published in the Journal of Neuroinflammation.

The new study, entitled “Rapid cognitive improvement in Alzheimer’s disease following perispinal etanercept administration,” and the accompanying commentary, entitled “Perispinal etanercept: Potential as an Alzheimer’s therapeutic,” are available on the Web site of the Journal of Neuroinflammation.

The case study highlighted is a single patient in a 15 subject non-placebo controlled off-label study of the Etanercept (Enbrel). Etanercept is a tumor necrosis factor-alpha (TNF) Antagonist, that is, it blocks the activity of TNF. The agent is a FDA approved for the treatment of various forms of arthritis. Etanercept was administered to the spine under the hypothesis that elevated levels of TNF interferes with neural transmissions in the brain.

Following administration of Enbrel in the subject, his cognitive faculties demonstrated marked improvement within minutes.

The Healing Project consulted with leading experts in drug development and Alzheimer’s disease who have reviewed the article. While only a single case, the methods and measures used on the subject paint a compelling case that a double-blind placebo controlled trial should be undertaken with sufficient power to answer the question whether Enbrel administered through the spine can produce similar results in a large population. Our experts caution, that factors regarding this patient (general health, lack of overlapping morbidities, large cognitive reserve etc.), would limit the likelihood that all patients in a larger trial could achieve a similar result. Further, the effect demonstrated in this patient was not likely to be disease modifying but a result of increased brain efficiency due to the relief of neural inflammation. In addition, the nature of Enbrel would limit its use across the broadest possible population. Finally, no inference can be made regarding Enbrel’s disease modifying properties without a carefully designed trial to answer that question.

A small number of experts have already chimed in dismissing the Alzheimer’s inflammation hypothesis. The dismissal is based upon studies that failed to demonstrate efficacy using NSAIDs. (This would further imply all drug development in dementia should be terminated based on all current theories of the disease. No compound has demonstrated efficacy or ecological validity.) There are numerous reasons why these agents failed to demonstrate efficacy and bear no relationship to TNF Antagonists. Keep in mind, many of these experts are conflicted due to their support of alternate theories of disease treatment, disease diagnosis and disease process. The attempt to summarily dismiss these results confirms why the progress in dementia research has been retarded for two decades.

It is essential that every reasonable avenue research be pursued to relieve Alzheimer's symptoms and hopefully identify a cure. Given our belief, that dementia better characterizes the loss of memory in aging, Enbrel, if proved efficacious, would be an element of a complex treatment protocol that would benefit a large subset of patients along the arc of the illness.