ZSD MOUSE MODEL PROJECTS
Eye disease model
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To better understand Zellweger Spectrum Disorder (ZSD) pathophysiology and test potential therapies in vivo, we participated in engineering the PEX1-G844D mouse model for mild ZSD, which bears the murine equivalent to the common human PEX1-G843D mutation. In our laboratory, we have characterized the progression of retinopathy in this model in collaboration with Dr. Pierre Lachapelle (McGill University), and continue with deep phenotyping efforts. Together with Dr. Jean Bennett (University of Pennsylvania) and Dr. Joseph Hacia (University of Southern California) we developed a PEX1 retinal gene therapy that improved visual function in PEX1-G844D mice, and won venture capital investment award based on our proof-of-concept studies. We continue to lead the preclinical development of this therapy towards clinical application with the support of our Montreal-based investors, AmorChem Therapeutics.
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Work published in Argyriou et al., 2019 and in Argyriou et al., 2021
Healthy control and PEX1-G844D mice received a subretinal injection of the normal PEX1 gene and a mock vector in their contralateral eye (lower left image). Localization of the injected PEX1-GFP protein can be visualized in the mouse retina with fluorescent microscopy (upper image). We conducted various visual function tests on the treated mice, including the optodrum test that measures visual acuity and constrast senstivity (lower right image). Images from Catherine Argyriou.
Liver disease model
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We have characterized the clinical picture of the liver disease in our PEX1-G843D mouse model in our laboratory. We are now treating the mice with compounds identified in the drug screening to look for improvement in liver disease. We are also investigating novel mechanisms of peroxisome pathophysiology for the liver disease (Lingxiao Chen).