(CN) — A milestone in Alzheimer’s disease research emerged Wednesday as scientists revealed an improved magnetic nanoparticle that alleviated the biological and behavioral symptoms of Alzheimer’s in mice.
The new study in Science Advances comes from a team of researchers who configured a new peptide-carrying magnetic nanoparticle to treat one of the major neuropathologic hallmarks of Alzheimer's disease: tangled fibrils of tau protein.
Tau proteins normally stabilize structures within the axons of neurons so that the nerve cells can communicate throughout an animal’s body. But with Alzheimer’s disease — a progressive and fatal neurogenerative disease — the protein is unable to regulate axon structures and aggregates into tangled clusters for reasons that are not entirely understood.
After 10 weeks of treatment on affected mice, the researchers say that their nanoparticle prevented the accumulation of tau fibrils inside neurons, disassembled protein buildup and prevented diseased neurons from spreading — all while allowing mice to improve in object recognition tests and maze challenges.
“We found the treatment of 7-DP–conjugated MNPs (MNPs-DP) reversed the behavioral deficits of PS19 mice, a model of AD tauopathy,” the researchers wrote in the study. “7-DP not only prevents tau aggregation but also dissolves existing tau aggregates.”
The findings follow up on an earlier magnetic nanoparticle developed by some of the same researchers at the Eisenberg Lab at the University of California Los Angeles-Department of Energy’s Institute for Genomics and Proteomics. That prototype carried a 6-residue, non-natural amino acid inhibitor peptide, which mediated tau accrual in vitro but failed to stop tau proteins from spreading cell-to-cell.
“We conjugated 7-DP to MNPs to facilitate its transport across the [blood brain barrier],” the researchers wrote, adding that brain-deliverable peptides that can fragment tau fibrils are promising precursors to potential Alzheimer’s disease therapies.
The study also represents progress in Alzheimer’s research when clinical trials targeting amyloid beta plaques — the other hallmark of the disease — have not lived up to their promise in treating the common and devastating disease.
“Our work supports future phase 1 evaluation of 7-DP formulations including MNPs-DP in humans with AD and other tauopathies,” the authors wrote. “If safe and acutely effective against tauopathy biomarkers, then this new class of highly specific structurally designed tau fragmentors could be optimized and further developed for clinical use."
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