Photo/Illutration Tokyo Medical and Dental University in Tokyo’s Bunkyo Ward (Asahi Shimbun file photo)

A team of scientists has developed a new method involving glucose and fragmented antibodies to better reduce an abnormal accumulation of protein in the brains of mice with Alzheimer’s disease.

The amyloid beta protein accumulation in the brain is believed to trigger Alzheimer’s.

The researchers, primarily from Tokyo Medical and Dental University and the Innovation Center of Nanomedicine, encapsulated fragments of an antibody that can attach itself to the protein and remove it from the brain into what they call nanomachine measured in nanometers.

They also attached glucose molecules to the surface of the nanomachine. 

This was done to make it easier for the brain to accept the antibody.

“We hope this accomplishment will lead to the development of a new therapy that is safer and more efficient than its conventional antibody-used counterpart,” said Takanori Yokota, a neurology professor at the university who was part of the team.

The researchers injected the encapsulated antibody fragments into mice marked by unusual amounts of amyloid beta due to the disorder. The agent’s administration was done weekly for 10 consecutive weeks.

The research showed that use of the nanomachine can deliver 80 times more volume of antibody fragments to the brain than injecting them directly.

It was also confirmed that lumps of amyloid beta can be removed using this method, which hampered the protein from congregating as well.

Previously, only part of the administered medicine to remove the protein could reach the brain because of a mechanism called the blood-brain barrier, which decides what to take in from blood vessels to protect the brain.

However, inspired by the fact that among materials necessary for the brain, glucose can pass through the blood-brain barrier in particularly large volumes, the team’s members committed themselves to developing a glucose-applied nanomachine with the medicine embedded into the macromolecular particles.

The drug incorporated into the nanomachine was then carefully adjusted.

The researchers decided to use fragments of the antibody because a whole antibody is too large to be embedded in large numbers.

An unexpected beneficial effect emerged as a result.

Therapeutic antibodies for Alzheimer’s disease are known for their side effect of causing, for example, brain swelling via inflammatory reactions.

The team expects this side effect could be averted as the fragmented antibody lacks the section responsible for inflammatory reactions.

The scientists’ findings were published on Jan. 31 in the international specialized magazine Journal of Nanobiotechnology at (https://doi.org/10.1186/s12951-023-01772-y).

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