Vianey Cardiel
Pronouns: She/They
Research Mentor(s): Andrew Lieberman
Research Mentor School/College/Department: Pathology / Medicine
Program: UROPF
Session: Session 4 (1:40pm – 2:30pm)
Authors: Vianey Cardiel, Ruth Azaria, Mark Schultz, Andrew Lieberman
Abstract
Niemann-Pick C is a rare neurodegenerative disease. The disease presents in childhood and causes progressive neurodegeneration until death. Niemann-Pick C is caused by loss-of-function mutations in the NPC1 gene, which encodes for a lysosomal cholesterol transport protein called NPC1. Mutations in NPC1 cause the protein to misfold and degrade before reaching the lysosome, resulting in cholesterol accumulation in the brain and other tissues. As Niemann-Pick C is caused by defects in a single gene, the disease a good candidate for gene therapy. While previous studies have shown that gene therapy using human NPC1 is effective at correcting some disease phenotypes in mice, our lab has shown that mouse NPC1 folds and traffics more efficiently than human NPC1. As a result, we hypothesized that mouse NPC1 will be a more effective gene therapy treatment for Niemann-Pick C disease than human NPC1. To test this hypothesis, NPC1-null mice were injected with AAV9 vectors expressing human NPC1, mouse NPC1, or green fluorescent protein (GFP) under the control of the Syn1 promoter (active in neurons). After treatment, motor skills and body weight of these mice are measured to determine the effectiveness of treatment in improving symptoms. Motor skills are tested by rota-rod and balance beam. Though testing is ongoing, initial data demonstrates that gene therapy with mouse and human NPC1 similarly improve disease phenotypes beyond control-treated NPC1-null mice.
