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Dr. Adriano Aguzzi and Davide Caredio

Grant Title: Investigation of Glycoprotein Nonmetastatic Melanoma protein B (GPNMB) as potential therapeutic target in Prion Diseases

Location: University of Zurich

Grant Year: 2024
The core of this study revolves around a protein named GPNMB, which has been found to protect neurons in the brain and lessen damaging inflammation often seen in prion diseases. A key issue, however, is that GPNMB typically increases only at advanced stages of the disease, when it’s usually too late to be effective. Remarkably, we have observed that introducing GPNMB into brain tissues in laboratory settings can guard them against the detrimental impact of prions. To translate this discovery into practical patient treatment, we propose a research work programme with two primary objectives. Firstly, we plan to use a cutting-edge genetic technology called CRISPR-Cas9 to activate each gene in human microglial cells, which are a type of immune cell in the brain, to identify which genes, when activated, lead to increased production of the GPNMB protein. The genes that show the most promise, especially those that could be targeted with medications, will be selected for further study. Secondly, we will test these selected genes in sophisticated lab models that more accurately mimic the way diseases damage the brain. The ultimate aim of this research is to discover new treatment methods that can boost GPNMB production early in the disease’s progression, providing stronger protection for the brain.

About the Researchers:

Dr. Adriano Aguzzi
Adriano Aguzzi has devoted his professional life to deciphering the role of the immune system in prion diseases. The importance of his work is acknowledged by almost 72’000 citations (H-index: 137). Aguzzi’s findings of pervasive colonization of the immune system by prions convinced governments worldwide to undertake efforts to limit human exposure to prions derived from farm animals. His finding of the B-cell requirement for prion spread was the basis of the UK’s decision to introduce universal leukodepletion of blood donation – a measure that is likely to have saved thousands of human lives. His work demonstrated that chronic inflammation controls the organ tropism of prion diseases, thereby clarifying how scrapie prions propagate horizontally within sheep flocks. The realization that prion excretion results from coincident inflammation and prion infection is paving the way to the eradication of prion diseases from ruminants. His discoveries were shown to be valid for all common neurodegenerative diseases including Alzheimer’s (AD) and Parkinson’s.

Davide Caredio
As a Ph.D. candidate at the University of Zurich under the guidance of Prof. Adriano Aguzzi, Davide is a dedicated researcher specializing in prion disease. His work is centered on deciphering the intricate mechanisms of these conditions, with a strong emphasis on identifying associated biomarkers and developing treatments. He possesses a deep expertise in cutting-edge techniques such as single cell RNA sequencing, spatial transcriptomics, and advanced genetic screening.

Recipient of:

Research Grants Supported

Robert C.C. Mercer, Ph.D.

Grant Title:
The identification of PrPSc interaction partners and the characterization of their role in prion infection and/or propagation

Location:
Instructor, Department of Biochemistry, Boston University School of Medicine

Grant Year: 2023