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Novel Drug Candidate to Treat Alzheimer's Identified
Researchers from Mental Health Research Institute of Victoria in Australia have identified compounds that could stimulate rapid improvement in cognitive function in mice with Alzheimer's disease.
Ionophore, a compound that transports metal ions across cell membranes, can elicit rapid and pronounced improvement in neuropathology and cognitive function of transgenic mice.
Recent studies had shown dysregulation of metal ions in the brain, particularly copper and zinc, in the pathogenesis of AD that also damages accumulation of amyloid beta (A?) protein, which is characteristic of this devastating disease.
The ionophore clioquinol (CQ), an 8-hydroxyquinoline, has been shown to increase intracellular copper and zinc levels and decrease A? levels in cultured cells and in the brains of transgenic (Tg) AD mice.
Researchers Dr. Ashley I. Bush with Dr. Paul A. Adlard and colleagues examined the therapeutic potential of PBT2, a second generation 8-hydroxyquinoline designed for easier synthesis, higher solubility and increased blood-brain barrier permeablility, in two well established Tg mouse models of AD.
"Both types of Tg mice exhibit progressive spatial learning deficits that are accompanied by increasing A? levels and plaque formation," said Bush
"Demonstrating benefits of PBT2 treatment in the two separate models was both a stringency test, increasing confidence that PBT2 is more likely to show benefit in clinical trials, and also allowed us to determine whether specific forms of A? change in register with cognitive improvement in both strains.
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