Alzheimer's: Antibody preparation eliminates plaques

Agent reduces beta amyloid deposits in the brain and improves dementia symptoms

Deposits of beta-amyloid proteins are thought to be the cause of brain cell death in Alzheimer's disease. © NIA / NOH
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Surprisingly effective: A new antibody drug can dissolve plaques in the brains of Alzheimer's patients. In one clinical study, the amount of clumped proteins dropped to almost normal levels after one year of treatment. The dementia symptoms of patients also improved, as the researchers report in the journal "Nature". Follow-up studies will now show whether this antibody preparation can actually slow down or even stop Alzheimer's dementia.

One of the typical symptoms of Alzheimer's disease is deposits of clumped proteins in the brain called plaques. Instead of being broken down, the beta-amyloid protein continues to accumulate in Alzheimer's patients. According to one of the hypotheses about Alzheimer's, these beta-amyloid plaques are the reason why brain cells die and patients become dementia.

Antibodies to plaques

"So far, however, all attempts have been unsuccessful to eliminate beta-amyloid with the help of immunotherapy or to mitigate its neurotoxicity, " explain Jeff Sevigny of Biogen and his colleagues. In immunotherapy, specific antibodies bind to the target protein, thereby marking it, for example, for disposal or preventing its clumping.

Now, however, a clinical trial with the antibody Aducanumab raises new hope. This monoclonal antibody had already been shown in mice to be effective against amyloid plaques. That's why Sevigny and his colleagues started a randomized and double-blind human study in the fall of 2012.

One infusion a month

For this study, 165 patients with mild Alzheimer's dementia and significant accumulations of amyloid plaques in the brain received monthly infusion of the antibody or a placebo solution. The dosages of the antibody varied between one, three, six or ten milligrams per kilogram of body weight. display

Degradation of the brain substance in middle and severe Alzheimer NIA

In the course of the study, the researchers reviewed the amount of beta-amyloid in the brain of patients using positron emission tomography (PET). After six months and one year, they again subjected all patients to tests of their mental performance.

Amyloid plaques greatly reduced

The result: After 54 weeks of treatment, the antibody therapy had surprised, as the researchers report. The amount of beta-amyloid in the brain of the patients had decreased significantly. The effect was the greater, the higher the antibody preparation had been dosed. In the placebo group, however, there was no change.

"In the highest dose group of ten milligrams per kilogram of aducanumab, the amyloid levels were close to the limit after one year, which is considered normal, " report Sevigny and his colleagues. Apparently, the antibody manages to penetrate from the blood into the brain, there specifically bind to the amyloid beta and eliminate both the soluble and the insoluble form.

Mental degradation slows down

More importantly, the decrease in amyloid plaques also improved the patients' dementia symptoms. As the tests showed after one year, the mental degradation was slowed down by the Antik rper gift. Also, a dose-dependent effect can be seen, the researchers report.

"These cognitive findings support the hypothesis that reducing beta-amyloid in the brain has a clinical benefit, " explain Sevigny and his colleagues. If one succeeds in eliminating the plaques and the soluble form of this protein, then also the mental degradation seems to decrease. The exact mechanism of this effect needs to be clarified.

Amyloid plaques in the brain of an Alzheimer's patient Nephron / CC-by-sa 3.0

Follow-up study has already begun

This is just a beginning yet ein but a promising one. "The results of this clinical study give us great confidence in taking a significant step forward in the treatment of Alzheimer's, " says co-author Roger Nitsch of the University of Zurich. "The effect of the antibody is impressive."

However, how well the remedy works against dementia in the long term and whether it may even stop or even stop Alzheimer's should now be shown in further studies. "These results justify the further development of Aducanumab as a treatment for Alzheimer's disease, " say the researchers. They report that a Phase 3 trial with this antibody and more than 2, 700 participants in 20 countries has already begun and is expected to deliver results by 2020.

"Behavior optimistic"

A cautious reason for hope is also seen by other Alzheimer's researchers in these results: "I am cautiously optimistic about this treatment, " comments Tara Spiers-Jones from the University of Edinburgh. "However, some drugs have already entered this early phase of clinical trials, only to fail in the larger follow-up studies."

Robert Howard of University College London agrees: "While this may potentially be an exciting story, it is important to look at it with caution, " he comments. "It would be premature to conclude that this is an effective cure for Alzheimer's disease - as much as we would like it to be." (Nature, 2016; doi: 10.1038 / nature19323)

(Nature, 01.09.2016 - NPO)