Alzheimer's Disease Research
Gary Landreth, Ph.D.
Case Western Reserve University
Cleveland, OH, United States
Title: RXR: A Therapeutic Target in Neurodegenerative Disease
Non-Technical Title: Rexinoids: New Therapeutic Agents for Alzheimer's Disease and Related Disorders
Duration: July 1, 2011 - June 30, 2013
Award Type: Standard
Award Amount: $250,000
A new rexinoid drug can rapidly remove existing plaques and lower Abeta peptide levels with improvement in memory and cognition within one week in amyloidogenic mouse models of AD. We propose to determine if this drug acts to prevent neuronal loss and dysfunction in two mouse models of neurodegeneration due to overproduction of Abeta or a mutant form of tau.
A drug that is taken by mouth has been shown to lower beta-amyloid levels and remove existing plaques in the brains of mouse models with Alzheimer's disease. In this research project, Dr. Gary Landreth and colleagues will be testing whether this drug also can prevent damage to brain cells in another type of Alzheimer's disease mouse. If it does have protective effects, it could be put on the fast track for human clinical trials. This drug holds particular promise due to its disease modifying actions.
Dr. Landreth’s team has used the first 9 months of funding to generate the animal models and personnel resources to carry out the study. The team has established a colony of Alzheimer’s disease mice (called 5XFAD) and let them grow to the age of 8 months—an older stage that is appropriate for testing therapies for Alzheimer’s. The team has conducted a pilot study in a few of these older mice to verify that they are experiencing age-related disease symptoms. In parallel, they have generated about 60 Alzheimer’s mice that range in age from 1-3 months. These mice, when of an appropriate age, will be used in the proposed experiments. Importantly, the team has recruited a postdoctoral fellow, Dr. Monica Holley, to carry out this project. She arrived April 1, 2012 and has already initiated the baseline analysis of the 5XFAD mice.
Dr. Landreth is a professor in the Department of Neurosciences at Case Western Reserve University. He received his undergraduate degree in chemistry and biochemistry from the University of Kansas in 1972. He then completed a Ph.D. in the Neurosciences Program at the University of Michigan, including a year of study at the National Institute of Medical Research in London. He did postdoctoral work in the Department of Neurobiology at Stanford. His work has focused on investigation of the biological basis of Alzheimer's disease and on drug development for this disorder.