Potential Alzheimer's antibody crosses blood-brain barrier in primates


A US study has shown that an antibody being explored for its potential to fight Alzheimer’s disease is capable of crossing the blood-brain barrier in non-human primates – a crucial part of developing treatments for the disease. The study was published yesterday (November 5) in the journal Science Translational Medicine.


The study, from researchers at San Francisco biotechnology firm Genentech, investigated an antibody that binds to an enzyme called BACE1, which is involved in the production of a hallmark Alzheimer’s protein called amyloid, or amyloid-beta. The scientists hypothesise that the antibody, which blocks the activity of BACE1, may be able to halt the production of amyloid, which accumulates in the brain and is thought to trigger Alzheimer’s disease.

In order for the antibody to reach its target in the brain, however, the team first needed it to cross the blood-brain barrier – a wall of cells that restrict which molecules can pass from the blood into the brain. To achieve this, they created a ‘bi-specific’ antibody that not only bound to BACE1 and blocked its activity, but also bound to a protein called transferrin receptor, which normally shuttles the protein transferrin across the blood-brain barrier.

The scientists tested this ‘dual action’ antibody in primates, and found that it was able to cross the blood-brain barrier without serious side effects. Further analysis showed that primates treated with the antibody had a decrease in the amount of amyloid-beta present in their cerebrospinal fluid and in the brain.

Dr Eric Karran, Director of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity, said: “A key challenge in Alzheimer’s drug development is ensuring that antibody treatments can be delivered to the brain in order to have an effect. This US study in primates highlights a method for increasing the penetration of antibody into the brain to reduce amyloid-beta production. Further research should investigate whether this method would be safe and effective for people. There are other drugs currently in clinical trials that target BACE1, and this alternative approach will need to undergo extensive testing to determine whether this treatment could help fight Alzheimer’s disease.

“Alzheimer’s is the most common cause of dementia, affecting half a million people in the UK, but current drugs aren’t able to affect the course of the disease. Investment in research is vital if we are to make a real different to people’s lives and find treatments capable of stopping this disease in its tracks.”


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