Title:

Investigating Lysosomes and Protein Degradation Pathways for the Treatment of Congenital Muscular Dystrophy Type 1A

Author: Smith, Sarah
Advisor: Dowling, James
Issue Date: Nov-2016
Abstract (summary): Congenital muscular dystrophy type 1A (MDC1A) is the most common congenital muscular dystrophy in Western countries. The goal of our lab is to identify potential therapies for MDC1A that can be translated into clinical use. Previously, we observed lysosome redistribution in muscle biopsies from human MDC1A patients. Here, we corroborate this observation by documenting lysosome redistribution to the myosepta in the zebrafish model of MDC1A, candyfloss (caf); however we show that manipulating the membrane-repair and membrane-fusion capacity of lysosomes with chemicals does not appear to have therapeutic potential. Alongside these experiments, we tested chemicals that had previously been explored in mouse models of MDC1A and found that MG132, a proteasome inhibitor, partially ameliorates disease pathology in caf mutants. Further investigation into the mechanisms by which MG132 functions in zebrafish, as well as targeting other aspects of lysosome function, will provide important insights into potential treatments for this debilitating muscle disease.
Content Type: Thesis

Permanent link

https://hdl.handle.net/1807/76035

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