Sometimes the finest things in life happen by coincidence, when we happen to be in the right location at the right moment. Now, Japanese researchers have discovered a method to ensure that new treatments are delivered to the proper area in the body and at the right moment in illness progression, ensuring that they have the greatest effect.
In a study published recently in the Journal of Nanobiotechnology, researchers led by Tokyo Medical and Dental University (TMDU) have revealed that a novel delivery system delivers treatment to where it is needed most 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, notably Ab oligomers (AbOs).
"Multiple clinical trials have attempted to use an anti-Ab antibody to treat AD, but the results have been unsatisfactory," said lead author of the study Akiko Amano, adding, "One potential explanation for this is that the blood-brain barrier (BBB) prevents most full-length antibodies from entering the brain."
To address this challenge, the researchers previously developed glucosylated (sugar-linked) polymeric nanomicelles (PMs), which are tiny, hollow balls 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 levels after the mice experienced fasting conditions. In this study, Takanori Yokota and colleagues filled PMs with fragments of an anti-AbO antibody, injected them into a mouse model of AD, and assessed the effects on the brain and on behavior.
"The results were very clear," said senior author Nobuo Sanjo, adding, "Administration of anti-AbO antibody fragments through PMs significantly reduced the amounts of various toxic Ab species. In addition, the Ab plaques that did form 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 the antibody fragment-filled PMs had better learning and spatial memory than untreated mice. "Our findings suggest that delivering sufficient levels of antibodies to the brain using PMs can reduce toxic Ab species and slow AD progression in mice," said Amano. (ANI)