Progress Updates
In Alzheimer's disease (AD), glial cells in the brain are over-activated and produce detrimental inflammatory molecules, called proinflammatory cytokines, which can contribute to nerve cell death and accelerate the progression of the disease. This raises the logical question of whether drugs can be developed to selectively target cytokine up-regulation, and thus reduce this abnormal increase in protein expression in glia, with the hope that such drugs would slow down or perhaps even prevent disease progression.
We have developed two drug-like compounds, named Minozac and Minokine that are safe in animals, can readily enter the brain, and are able to be taken by mouth. We have found that these compounds restore the glial cytokine production back towards normal levels, which prevents subsequent nerve cell damage and learning deficits in an animal model of early stage AD.
Our BrightFocus project is extending these findings to test Minozac and Minokine for effectiveness in a more severely affected AD transgenic mouse model, in order to ask whether the compounds are effective not only at preventing or suppressing cytokine-driven neurologic damage in early stages, but are also effective under conditions of increased disease severity. In the first two years of the project, we have completed the synthesis and quality control for both Minozac and Minokine, have validated the upregulation of proinflammatory cytokine production in an AD transgenic mouse model, and have begun testing compound efficacy. Successful completion of this project will provide a compelling rationale for further development of these compounds into future, potentially disease-modifying drugs for Alzheimer's disease.
