Scientists report a remarkable improvement in Alzheimer's transgenic mice following treatment with a new drug. The study, published by Cell Press in the July 10th issue of the journal Neuron, provides the first demonstration that an ionophore, a compound that transports metal ions across cell membranes, can elicit rapid and pronounced improvement in neuropathology and cognitive function in mouse models of Alzheimer's Disease (AD).
Recent research has implicated dysregulation of metal ions in the brain, particularly copper and zinc, in the pathogenesis of AD and the damaging accumulation of amyloid beta (Aâ) protein that 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 Aâ levels in cultured cells and in the brains of transgenic (Tg) AD mice. However, further studies in mice and humans demonstrated that brain entry of CQ was quite limited.
Dr. Ashley I. Bush from the Mental Health Research Institute of Victoria in Australia, 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 permeability, in two well established Tg mouse models of AD. The Tg mice examined in the study overexpress the precursor protein for Aâ and possess mutations that cause AD in humans. One of the Tg models also expresses the human presenilin deletion mutation that also causes AD.