MicroRNA-145-targeted drug and its preventive effect on pulmonary arterial hypertension (patent WO2012153135 A1)

Expert Opinion on Therapeutic Patents
Natalia Ogorodnikova, Christoph Arenz

Abstract

Pulmonary arterial hypertension (PAH) is a disease of various etiologies, characterized by progressive vascular remodeling that leads to right ventricular hypertrophy and heart failure. Although modern therapy improves life quality of patients, prognosis of PAH remains poor with a high mortality rate. Overexpression of microRNA (miR)-145, which was found in PAH patients, leads to progression of vascular remodeling. The current patent proposes a strategy using antisense oligonucleotides (ASOs) against miR-145 for prevention and treatment of PAH. Overexpression of miR-145 was shown in chronic hypoxia mouse models and PAH patients. Genetic ablation of miR-145 in hypoxic mice led to improved hemodynamic and vascular remodeling parameters. Furthermore, miR-145 inhibition by ASOs has been performed in chronic hypoxia mouse models. The experiments showed improved systolic right ventricular pressure and a decreased percentage of vascular remodeling. Although the mouse model does not display the full pathology of PAH, the inhibition of miR-145 by modified ASOs is promising for prevention and reversion of vascular remodeling. Whether such ASOs can be efficiently delivered and will prevent progression of PAH pathology and may lead to an e...Continue Reading

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Citations

Dec 15, 2015·Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology·Saumya BansalKenneth B Storey
Apr 5, 2018·Frontiers in Pharmacology·Yu WangLizhong Du

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