A Play-by-Play Explanation of New Research on the Prevention of Alzheimer's

David Roeltgen, MD Health Guide
  • In my most recent blog, I reviewed the concepts of phase 1, phase 2 and phase 3 research trials and briefly summarized the results from a recent phase three study of a drug called tramiprosate. Today, I'd like to focus on an exciting, new, and potentially important phase 1 study.

     

    As I indicated, phase 1 is the earliest and most basic level of research, designed to evaluate whether the proposed research is do-able. It can also be called a "proof of concept" study. Researchers from the University of Rochester Medical Center, led by Berislav Zlokovic, M.D., Ph.D., have taken a novel approach in trying to diminish the amount of amyloid-beta in the brain. Readers of this blog and readers who monitor research in Alzheimer's disease are aware that amyloid-beta, a protein that is produced in the brain, has a major role in the progression of Alzheimer's disease. Amyloid-beta forms toxic plaques that were described by Alzheimer in his original description of the disease.

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    Interest in them remains high because of their apparent role in causing some of the impairments in brain function that are present in patients with that disease. In this context, a major thrust of research in evaluating forms of treatment for Alzheimer's disease has been to develop methods by which the amyloid-beta in the brain can be reduced.

     

    Zlokovic and colleagues discovered a protein that is present in the blood (soluble low-density lipoprotein receptor related protein) (LRP) where it binds to and neutralizes large amounts of amyloid-beta. In any mouse model of Alzheimer's disease, where amyloid-beta is part of the problem, these researchers have used a protein similar to LRP to diminish the amyloid-beta. In doing this they showed that the mice treated in this way did not show the progression of the disease as did the mice that were not treated.

     

    Zlokovic and colleagues have found that the amounts of LRP are diminished in Alzheimer's patients and abnormal LRP is more common in Alzheimer's patients than in people without the disease. In response to this finding, they developed a modified LRP, LRP-IV. In the mouse model of Alzheimer's disease, LRP-IV is even more efficient at decreasing the amyloid-beta in the mouse brain than is LRP. Additionally the animals treated with LRP-IV show improved learning and memory compared to animals not treated. Currently this research group is working on the development of a product that can be tested in a phase 1 study for people.

     

    There is an equilibrium, or balance between the amount of amyloid-beta in the brain and in the blood. The concept behind the approach described above is that if a product is present in the blood that can tightly bind within the blood to a toxic substance in the brain, it can then help remove that toxic substance from the brain. The product can do this by pushing the equilibrium in the direction of the blood, especially if either that product can be given in large amounts or, once it is attached to the toxic substance, removed from the body and replaced by new amount of that product. This approach of leaching or sucking a substance out of the brain in order to treat brain disease has been available for many years in other disorders, including accumulation of lead or copper in the brain.

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    Medication can be added to the blood in patients who have excessive lead or copper in the brain. The medication binds to the lead or copper in the blood and is then removed from the body when it is eliminated by the kidneys. Fresh medication can then be added that will again "suck" the offending chemical from the brain. The hope in the research approach by the team from the University of Rochester is that Alzheimer's disease can be treated in a similar fashion. They are currently early in the course of attempting to determine if this will happen. Though, all medical breakthroughs begin as phase 1 studies, so there's reason to have hope.

Published On: August 15, 2007