Sometimes the best things in life happen by chance when we happen to be in the right place at the right time. Now, Japanese scientists have discovered a method to ensure that new treatments are delivered to the right area of the body and at the right time in the progression of the disease, ensuring that they have the greatest effect.
In a study recently published in the Journal of Nanobiotechnology, researchers led by Tokyo Medical and Dental University (TMDU) revealed that a new delivery system delivers treatment where it is most needed in a mouse model of Alzheimer’s disease (AD).
AD is a common neurodegenerative disease that causes dementia. It is characterized by the accumulation of a protein called amyloid b (Ab) in the brain, and a number of different toxic forms of Ab have been identified that impair brain function, particularly Ab oligomers (AbOs).
“Several clinical trials have attempted to use an anti-Ab antibody to treat AD, but the results have been unsatisfactory,” said study lead author Akiko Amano, adding, “One possible explanation is that the blood-brain barrier (BBB) prevents most full-length antibodies from entering the the brain.
To address this challenge, researchers previously developed glucosylated (sugar-linked) polymeric nanomicelles (PMs), which are small hollow spheres that could successfully cross the BBB via transcytosis in mouse brain capillary endothelial cells; this process was mediated by glucose transporter-1 and induced by an increase in blood glucose after the mice experienced fasting conditions. In this study, Takanori Yokota and colleagues loaded PM fragments of an anti-AbO antibody, injected them into a mouse model of AD, and evaluated the effects on the brain and behavior.
“The results were very clear,” said lead author Nobuo Sanjo, adding, “Administration of anti-AbO antibody fragments via PM significantly reduced the amount of various toxic Ab species. Furthermore, the Ab plaques that formed were smaller and less dense than those seen in untreated mice.
Next, the researchers analyzed the mice’s behavior and found that mice treated with PM loaded with antibody fragments had better learning and spatial memory than untreated mice. “Our findings suggest that delivering sufficient levels of antibodies to the brain using PM can reduce toxic Ab species and slow the progression of AD in mice,” Amano said.
