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Pulmonary disease

Pulmonary fibrosis

Rho kinase; myocardin-related transcription factor A (MKL1; MAL; MRTF-1)

Human tissue and mouse studies suggest inhibiting Rho kinase or MKL1 could help treat pulmonary fibrosis. Pulmonary myofibroblasts from patients with idiopathic pulmonary fibrosis (IPF) or a mouse model for lung fibrosis had greater activation of Rho kinase signaling than myofibroblasts from uninjured controls. In a mouse model for lung fibrosis, the Rho kinase inhibitor Eril fasudil or knockout of Mkl1 decreased fibrosis compared with saline or no knockout. Next steps include finding a partner to start Phase II studies of Rho kinase inhibitors in patients with IPF.
Eril is marketed by Asahi Kasei Pharma Corp. to treat aneurysm.
At least four other companies have Rho kinase inhibitors in preclinical development to Phase III trials for ophthalmic, pulmonary and cardiovascular indications.

SciBX 6(10); doi:10.1038/scibx.2013.244
Published online March 14, 2013

Unpatented; licensing status not applicable

Zhou, Y. et al. J. Clin. Invest.;
published online Feb. 22, 2013;
Contact: Victor J. Thannickal,
The University of Alabama at Birmingham, Birmingham, Ala.
Contact: Yong Zhou, same affiliation as above