RXR: A Therapeutic Target in Neurodegenerative Disease

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.

Progress Updates

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.