Targeting thromboxane/TP and prostaglandin D2/DP2 signaling with KAR101 may reduce lung inflammation, fibrosis and cardiopulmonary dysfunction in silicosis.
Quartz countertops are popular for their low maintenance and durability. Quartz is an engineered stone comprising 95% silica particles bound together with resins. Cutting and fabricating of quartz leads to release of silica dust into the air that are inhaled and cause inflammation, damage and scarring of the lungs. Silicosis, in its most severe form, presents as progressive massive fibrosis requiring lung transplantation. Silicosis primarily affects young otherwise health individuals from minority groups, especially immigrant workers. There is currently no treatment for silicosis. In the mouse model of silicosis, treatment with ramatroban following silica instillation effectively reduce inflammation, cardiopulmonary dysfunction, and scarring in the lungs. Therefore, ramatroban is a potential treatment for silicosis and awaits testing in phase 2 clinical trials.
Pang and colleagues tested ramatroban in silicosis model constructed by a single intratracheal instillation of 8mg silica in 40µL PBS in male C57BL/6J mice of 8-10 weeks old. Pang et al, Theranostics, 2021, doi: 10.7150/thno.47627
Ra=ramatroban; Crs=compliance of the respiratory system
RVSP=right ventricular systolic pressure; RVHI= right ventricular hypertrophy index
Ramatroban has been used for the treatment of allergic rhinitis in Japan for over 20 years, and therefore, has an excellent safety profile. Given the efficacy of ramatroban in reducing fibrosis, inflammation and cardiopulmonary dysfunction in the silicosis mouse model, we are looking to conduct clinical trials of ramatroban in patients with silicosis.