Ace-tRNA readthrough therapy for choroideremia caused by nonsense mutations
Awardee: David M. Gamm
Institution: University of Wisconsin-Madison
Grant Amount: $64,360
Funding Period: February 1, 2022 - January 31, 2023
Summary:
Choroideremia is a devastating eye disease that leads to progressive loss of vision in 1 in 50,000 males. Currently, there are no approved treatments available for individuals affected by choroideremia. While several research laboratories are working on identifying effective therapies, such work is challenged by the lack of appropriate disease models that would allow clear assessment of the efficacy of a potential therapy. To overcome this impediment, the Gamm lab has developed induced pluripotent stem cell (iPSC)-derived retinal cell and organoid models, which provide a powerful platform for therapeutic testing. As in many other inherited disorders, choroideremia is commonly caused by “nonsense” mutations that prevent formation of full-length functional proteins. The Ahern lab has designed a specialized molecule that allows read-through of many types of these mutations, resulting in full-length protein production. Our goal is to test these read-through molecules in iPSC-derived retinal pigmented epithelial cells and photoreceptors affected by choroideremia in order to advance a new type of therapy for a significant portion of choroideremia patients.