Novel Drug Candidate to Treat Alzheimer's Identified

Researchers have identified a new drug candidate, called PBT2 that can effectively treat Alzheimer's disease, and improve cognitive function to boot.

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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.

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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

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"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.

"This is significant as cognitive loss in AD is not just a simple product of rising A? levels," he added.

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PBT2 was shown to be a superior ionophore when compared to CQ and the researchers went on to test A? levels and cognitive outcomes after oral treatment with PBT2.

"We found that oral treatment with PBT2 induced a dramatic improvement in learning and memory in both Tg models of AD, accompanied by a marked inhibition of AD-like neuropathology," said Bush

"These outcomes were rapid, with reduction of soluble interstitial A? occurring within hours, and significant cognitive benefits seen within days of first administration of the compound," he added.

Recent clinical trials in AD patients taking oral PBT2 have been promising and support PBT2 as a viable treatment for AD.

The study has been published by Cell Press in the July 10th issue of the journal Neuron.

Source-ANI
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