Alzheimer’s agents floppten: Now the research is taking a new path

It was the great hope for the research into Alzheimer’s disease: antibodies against the responsible protein Plaques should stop the brain deterioration. But so far, all of the agents failed in patients-Tests. Now, science relies on other attack goals against Forgetting.

It’s not often that a new substance to withstand the test phase, and never on the market. In the case of some medications this is not only associated with enormous financial losses, there is also a huge disappointment, especially for patients.

Such setbacks were recently in the case of several active compounds against Alzheimer’s disease, that doctors and Affected a breakthrough in the therapy of the most common Form of dementia, had hoped: antibodies should eliminate the typical protein deposits in the brain and the cognitive capacity of the patients improve.

The euphoria of the past few years is gone

Even in 2017, there were euphoric reports from the Alzheimer’s disease research, that 35 new drugs were in the Pipeline, which would pass through in the coming years, studies in patients. An overview of work from the year 2018 by Jeffrey Cummings of the Lou Ruvo Center for Brain Health in Las Vegas listed even 112 substances that have been tested at the time of the patient. The Alzheimer’s specialist was optimistic that out of these trials, active ingredients would go, might be necessary to stop the Forgotten. Getty Images/iStockphoto/Ralwel

But it is precisely this, a number of promising compounds have failed, most recently the antibody Aducanumab, since the first laboratory experiments, great hopes rested. The last major studies prior to market approval, in which 2700 patients should participate, were prematurely aborted. The participants may not improve memory, reminder, or well-being was to register.

Tested medications bring no improvement in Alzheimer’s symptoms

Similar disappointing results were the initially promising antibody Gantenerumab, Solanezumab or Crenezumab. Even if the agents were able to reduce the infamous Amyloid-Beta Plaques in the brain, there was no change in the symptoms, and the condition of the patient.

Hans-Ulrich Demuth, Deputy Director of the Fraunhofer Institute for cell therapy and immunology (IZI) in Leipzig, a little surprised. “The research is based on a more than 30-year-old theory that Amyloid-triggering Plaques of Alzheimer’s disease and its symptoms. However, the deposits consist not only of error, Protein-fragments, but also a lot of other cell scrap. And they are more or less active.“

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Were directed to the antibody against the wrong target?

Effective antibodies may not be directed, therefore, against the Plaques as a Whole, but only against the actually neurotoxic soluble Amyloid-Beta variants of these Plaques and in the cerebral fluid.

“But because of the previously tested anti-body paint only a small part can penetrate the blood-brain barrier, is not a sufficiently large concentration in the brain, the concentration of toxic Amyloid-Beta variants are clear, which are still soluble.”

For Alzheimer’s researchers, the development of such antibodies would have to be operated, the target this dangerous group of Amyloid-Beta. “At the beginning of the disease, relatively little of it is in the brain. In contrast, the small amount of antibody would be sufficient for the agent that can cross the blood-brain barrier.“ As a consequence, would have to also improve cognitive performance.

1. Antibodies directed against toxic Protein fragments

The biochemist, here are two research approaches from Germany as a promising (“There are in the world but much more.”):

• A small molecule (small molecule) against toxic Amyloid-Beta, developed by the Biotech company Probiodrug. “A Phase 2a study with 120 patients failed to demonstrate a cognitive improvement.” (Editors ‘ note: This company was co-founded by Hans-Ulrich Demuth.)
• At the Helmholtz research center Jülich, peptides to be tested, to prevent agglomeration of aggressively toxic Amyloid-Beta.

Early therapy is the key, regardless of the active ingredient

Some Alzheimer’s researchers believe that the antibodies have all failed because they were tested on patients in whom the disease was already advanced. The largest opportunities for Anti-Alzheimer’s medication, when used in a very early stage of the disease. If neurons are destroyed in the brain, it can no longer undo.

2. Antibody anti-coagulated proteins Inside the nerve cells

This is also true for therapeutic approaches, which devote themselves to the Tau protein. These molecules sit Inside the nerve cells and are regarded for some time as a possible trigger for Alzheimer’s. However, Tau proteins are involved in various brain diseases and non-Alzheimer’s disease-specific. Hans-Ulrich Demuth says: “When Tau proteins clump together and be deposited, broken neurons. At the beginning of the toxic Amyloid-Beta molecules, but in Alzheimer’s disease. You would be eliminated, Tau-proteins to disease development.“

Against the agglomeration of Tau proteins antibodies and small molecules are also in development. A first Phase 3 trial with an Anti-Tau drug, however, failed. The active ingredient of methylene blue was used against Malaria, but should be further tested.

3. Inflammation combat and Alzheimer’s disease slow down

A third, yet little is persecuted therapeutic approach against Alzheimer’s disease is based on the assumption that inflammatory processes are involved in Alzheimer’s disease. It was, according to Demuth is possible that chronic inflammation may trigger in the body Alzheimer’s. “The blood-brain barrier neurotransmitters that send out such inflammation can happen.”

It is proved the connection of inflammation in the body and the risk of Alzheimer disease: Who’s in the middle of the year high values, for example, of the inflammatory marker CRP (C-reactive Protein), has years later, there is an increased risk of Alzheimer’s. It is therefore important, especially chronic inflammation of the cushioning processes due to anti-inflammatory agents and reduce inflammatory markers. “Less inflammation get signals to the brain and that Alzheimer’s risk can be reduced”, explains Hans-Ulrich Demuth.

So long as the research has not made the long-promised breakthrough in Alzheimer’s therapy, is the risk-minimization in any case particularly important – and also through physical, mental and social activity.