New drug against Alzheimer's disease shows great promise
According to the results of recent studies, one of the components of the pathogenesis of Alzheimer's disease and the accumulation of beta-amyloid protein in brain tissue is a violation of the regulation of the level of metal ions, especially copper and zinc, in brain tissue. There is evidence that the ionophore (a molecule that ensures the movement of a metal ion through the membrane) clioquinol – clioquinol, CQ (nomenclature name – 8-hydroxyquinoline, 8-hydroxyquinoline) increases the intracellular content of copper and zinc ions and reduces the aggregation of beta-amyloid in cell cultures and brain cells of transgenic mice with Alzheimer's disease. However, further studies in mice and humans have demonstrated that the penetration of clioquinol into brain tissue is very limited.
Australian scientists at the Victoria Institute of Mental Health Research, working under the guidance of Dr. Ashley I. Bush, analyzed the therapeutic potential of PBT2, a second-generation 8-hydroxyquinoline drug developed to facilitate synthesis, increase solubility and the ability to penetrate the blood-brain barrier, on two lines of transgenic mice that are models of Alzheimer's disease. The genetically modified animals used by the authors show hyperexpression of the beta-amyloid precursor protein; in addition, they carry other mutations associated with Alzheimer's disease in humans. In both lines of mice, there is a gradual development of spatial learning disorders, accompanied by an increase in the level of beta-amyloid and the formation of plaques.
PBT2 is a more effective ionophore than clioquinol. During the experiments, the authors found that oral administration of PBT2 induces a marked improvement in the ability to learn and memorize in both mouse models of Alzheimer's disease, which is accompanied by a noticeable decrease in the neuropathology associated with Alzheimer's disease. These effects manifested themselves very quickly: a decrease in the level of the soluble intermediate form of beta-amyloid occurred within a few hours, and a significant improvement in cognitive function occurred within a few days after the first intake of the compound.
Moreover, the results of recent clinical trials of the oral form of PBT2 are promising and indicate the prospects of this drug in the treatment of Alzheimer's disease.
The results obtained support the need to continue testing compounds acting on synaptic ion levels as a treatment for Alzheimer's disease.
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily
14.07.2008