Genetic Prion Disease by James Mastrianni

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

Rebekah C. Evans, Ph.D., Georgetown University
In Vivo and Ex Vivo Dissection of Midbrain Neuron Activity During Exercise
Exercise is important for the health of the body and the mind. Exercise promotes learning and reduces symptoms of brain-related diseases such as Parkinson’s disease and Alzheimer’s disease. However, it…
William J. Giardino, Ph.D. Stanford University
Deciphering the Neuropeptide Circuitry of Emotional Arousal in Narcolepsy
This research project aims to investigate the neural mechanisms of a specific type of brain cell called neuropeptide neurons within a region of the brain’s amygdala network called the bed…
Howard Gritton, Ph.D., University of Illinois
Attention Mechanisms Contributing to Auditory Spatial Processing.
Our world is composed of a rich mixture of sounds. We often process sounds including speech in the presence of many other competing auditory stimuli (e.g., voices in a crowded…
Nora Kory, Ph.D., Harvard University
Elucidating the Fates and Functions of Lactate in the Brain
The human brain requires significant energy to function. Despite accounting for only 2% of our body weight, the brain consumes a substantial 20% of the body’s energy, relying on a…