Genetic Prion Disease

Treatment of Genetic Prion Disease by Mutation-Selective RNAi
2011 Seed Grant
James Mastrianni, M.D., Ph.D.
Department of Neurology
University of Chicago

Prion diseases are neurodegenerative diseases caused by the generation of a misfolded form of the prion protein (PrP). Genetic mutations within the PrP gene act to destabilize PrP, causing it to misfold into an abnormal shape. This misfolded PrP accumulates and causes neuronal toxicity. While everyone carries two copies of every gene, only one copy of the PrP gene is mutated in genetic prion diseases. In this study, we will attempt to alleviate the development of prion disease using a transgenic mouse model of genetic prion disease developed in our lab. We will specifically inhibit the mutated gene to significantly reduce the levels of only the mutated PrP, leaving non-mutated PrP unaffected. This targeted gene-therapy will be tested in cultured cells, then neuronal cultures from our transgenic mice, and then in live mice. These studies will be used as the foundation for strategies to treat genetic diseases in humans.

Other Grants

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The Role of Microglial Lysosomes in Selective Neuronal Vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
How the Nervous System Constructs Internal Models of the External World
As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the Orchestra of Movement—Functional Role of Striatal Astrocytes in Health and Disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…