Transporting antibodies across the blood-brain barrier to treat Alzheimer’s disease – ScienceDaily

Sometimes the best things in life come by accident, when we are in the right place at the right time. Now, researchers from Japan have found a way to ensure that new drugs reach the right place in the body and at the right time in the progression of the disease, so that they have the best effect.

In a study recently published in Journal of NanobiotechnologyIn a mouse model of Alzheimer’s disease (AD), researchers led by Tokyo Medical and Dental University (TMDU) have revealed that a new delivery system delivers treatment to where it is needed most.

Alzheimer’s is a common neurodegenerative disease that causes dementia. It is characterized by the accumulation of a protein called amyloid-β (Aβ) in the brain, and a number of different toxic forms of Aβ have been identified that impair brain function, in particular Aβ oligomers (AβOs).

“Several clinical trials have attempted to use an anti-Aβ antibody to treat Alzheimer’s disease, but the results have been unsatisfactory,” says Akiko Amano, lead author of the study. “One possible explanation for this is that the blood-brain barrier (BBB) ​​prevents most full-length antibodies from entering the brain.”

To address this challenge, researchers have previously developed glucosylated (sugar-bound) polymeric nanoparticles (PMs), which are small, hollow spheres that can successfully cross the BBB via cytokinesis in capillary endothelial cells in the mouse brain. This process was mediated by glucose transporter 1 and was induced by an increase in blood glucose levels after the rats experienced fasting conditions. In this study, Takanori Yokota and colleagues filled PMs with anti-AβO antibody fragments, injected them into a mouse model of Alzheimer’s disease, and evaluated the effects on the brain and behavior.

“The results have been very clear,” explains senior author Nobuo Sanjo. “Administration of anti-AβO antibody fragments through PMs significantly reduced the amounts of the various toxic species of Aβ. In addition, the Aβ plaques that formed were smaller and less dense than those seen in untreated mice.”

Next, the researchers analyzed the behavior of the mice and found that the mice treated with antibody-filled particles had better spatial learning and memory than the untreated mice. “Our findings indicate that delivering sufficient levels of antibodies to the brain with PMs can reduce toxic Aβ species and slow the progression of Alzheimer’s disease in mice,” says Amano.

Given that the failure of anti-Aβ antibodies to improve cognitive function in human clinical trials was most likely due to a lack of antibody supply in the brain, PM-encapsulated antibody fragments could represent an effective method to prevent the progression of AD. In addition, new candidates for an Alzheimer’s treatment that degrade toxic Aβs and reduce their toxic effects to the brain could also be offered using the same PM-based system.

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