Paolo Rossi Castelli 16 December 2021 5 min read

Two new strategies to fight Alzheimer’s disease

A vaccine has been developed in Boston that stimulates lymphocytes to remove affected beta amyloid protein plaques typical of Alzheimer's disease. Another international team wants to block soluble forms of the same protein.

The European Medical Agency has refused the use of aducanumab, the monoclonal antibody produced by U.S. company Biogen to destroy the altered amyloid beta protein plaques found in Alzheimer's dementia. However, Aducanumab, was approved by the US Food and Drug Administration on 7th June, despite the opposition of some of the deciding committee members, which was followed by their resignation.

In short, the situation appears to be in flux. It remains to be seen how U.S. insurance companies will reimburse this very expensive therapy and, considering the situation from a wider perspective, other strategies to combat Alzheimer's worldwide have proved difficult to implement for many years now. This is why news from those who are using new approaches to fight the disease (which currently has no effective treatment) is very interesting.

Just a few days ago, Boston’s Brigham and Women's Hospital announced the first phase of trials of a vaccine to be administered nasally on humans. This is the result of research that began over 20 years ago and has produced a huge amount of preclinical data. The vaccine focuses on a class of molecules called Protollin, extracted from bacteria, which have already been used as immunomodulators and adjuvants for other vaccines for years. Recent findings report that these molecules can trigger an immune response in lymph nodes on the sides and back of the neck, stimulating the production of lymphocytes that migrate to the brain and remove beta amyloid plaques in their early stage.

A trial for the over-60s
The vaccine will be tested on 16 people between 60 and 85 years of age who are showing early signs of Alzheimer's disease but have no other significant illnesses. The trial will assess the safety and tolerability of the vaccine, as well as studying its real effectiveness, through a detailed analysis of how it acts on the participants’ immune system.

A focus on truncated forms
Alternative strategies to fight Alzheimer's are the focus of a study by a team of British and German researchers, published in the journal of Molecular Psychiatry, which is part of the Nature group.

The study centred not on plaques, but on a soluble form of beta amyloid. So how does it work? Soluble beta amyloid is present in Alzheimer’s sufferers in truncated, shorter-than-normal forms. These combine to form filaments that are then deposited and damage brain cells. Researchers decided to disrupt this process using an antibody. This causes these molecules to fold, transforming them into a form that has never been reported before and is potentially extremely interesting. The researchers studied the folded protein, stabilised it and turned it into a highly specific antigen (a target) for the immune system, so that it works as a vaccine that can generate natural antibodies.

Two different animal trials have shown clear signs of improvement. Researchers and now looking for partners to start the first phases of trials on human volunteers.

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Paolo Rossi Castelli

Journalist since 1983, Paolo has been dealing with scientific divulgation for years, especially in the fields of medicine and biology. He is the creator of Sportello Cancro, the site created by corriere.it on oncology in collaboration with the Umberto Veronesi Foundation. He collaborated with the pages of the Science of Corriere della Sera for several years. He is the founder and director of PRC-Comunicare la scienza.