Prion disease is a fatal neurodegenerative disease caused by misfolding of the prion protein (PrP). Lowering PrP by genetic deletion or pharmacologic means both delays onset and slows progression of prion disease in animal models. We have developed a drug candidate for prion disease based on divalent siRNA technology, have completed the manufacturing of this drug and filed an Investigational New Drug application with the U.S. Food and Drug Administration. The purpose of this project is to launch first-in-human clinical trials of this divalent siRNA for prion disease in newly diagnosed symptomatic prion disease patients.
The primary objective is to evaluate safety and tolerability of the drug. The secondary objectives are to evaluate the pharmacodynamic impact — lowering of prion protein in cerebrospinal fluid (CSF), and concentration of drug in CSF and blood. The exploratory objectives are to measure disease-related biomarker and clinical endpoints. This project also includes an observational study of newly diagnosed symptomatic patients not treated with drug, to determine the longitudinal trajectory of biomarkers in this population as a comparator for this and future trials.