The Therapeutic Effects of Ataluren on BMPR2 Nonsense Mutations Leading to Pulmunary Arterial Hypertension

Date of Award

Spring 2015

Department

Biology

First Advisor

Dr. James Lissemore

Abstract

Pulmonary arterial hypertension is a serious disease caused by proliferation of arterial lung cells which constrict blood vessels, eventually leading to high blood pressure and heart failure. Nonsense mutations in the BMPR2 gene are the primary cause of this disorder, and currently no treatment is available. Ataluren is an experimental drug that has shown potential for being able to read-through nonsense mutations and restore gene expression and protein function. In this study, we introduced nonsense mutations into the BMPR2 gene. Plasmids carrying the BMPR2 mutant genes were nucleofected into pulmonary artery endothelial cells which were then treated with Ataluren. Flow cytometry data showed that Ataluren increased BMPRII expression to varying degrees for all mutations studied and showed a stronger effect for UGA mutations compared to UAG and UAA. These results show that Ataluren may be an effective therapeutic treatment for pulmonary arterial hypertension by promoting read-through of BMPR2 nonsense mutations.

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