Researchers at Beijing’s National Center for Nanoscience and Technology and colleagues published a paper in Nature Communications describing a self-destructive "nanosweeper" based on multifunctional peptide-polymers that improved memory deficits after capturing and degrading extracellular deposits of beta amyloid in the brains of mice, suggesting a potential new strategy to treat Alzheimer's disease.
Recent clinical data for several anti-beta amyloid mAbs, including solanezumab (LY2062430) from Eli Lilly and Co. (NYSE:LLY), have not shown a correlation between plaque clearance and cognitive benefit (see BioCentury, Dec. 16, 2016).
The researchers designed a nanosweeper comprising two main peptides: PEGylated GKLVFF, which recognizes and binds beta amyloid 42, and beclin 1 (BECN1; ATG6), which induces autophagy. The nanosweeper first captures and co-assembles with extracellular beta amyloid, thus inhibiting the formation of toxic beta amyloid aggregates. Next, the nanosweeper delivers beta amyloid into cells and activates autophagy within them to degrade the protein, clearing beta amyloid deposits.
In a transgenic mouse model of AD, the nanosweeper given every other day for one month decreased beta amyloid plaque load in brain tissue and attenuated neuron loss compared with no treatment.
The researchers then used the Morris water maze test to evaluate the spatial cognitive performance of the nanosweeper-treated mice. AD mice treated with the nanosweeper showed significantly shorter latency and increased spatial memory compared with control mice.
Additionally, hematology and histopathology assays showed that the nanosweepers did not lead to any systemic toxicity and could be safely used as a biomaterial to potentially treat AD.