Ramatroban (KAR101) as a potential treatment for silicosis
Targeting thromboxane/TP and prostaglandin D2/DP2 signaling with KAR101 may reduce lung inflammation, fibrosis and cardiopulmonary dysfunction in silicosis.
What is Silicosis?
Silicosis is a fibrotic lung disease caused by silica dust inhalation
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.
Silicosis is a major public issue affecting minority immigrant workers and there is no treatment.
Ramatroban in the Silicosis mouse model
PGD2 and TxA2 synthase are significantly upregulated in the lungs of patients with silicosis
PGD2 and TxA2 synthase are significantly upregulated in the lungs of patients with silicosis
PGD2 and TxA2 synthase are significantly upregulated in the lungs of patients with silicosis
Multi-omics study of silicosis reveals the potential therapeutic targets PGD2 and TXA2
PGD2 and TxA2 synthase are significantly upregulated in the lungs of patients with silicosis
PGD2 and TxA2 synthase are significantly upregulated in the lungs of patients with silicosis
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
PGD2 and TXA2 were significantly increased in silicosis mouse lungs
PGD2 and TxA2 synthase are significantly upregulated in the lungs of patients with silicosis
PGD2 and TXA2 were significantly increased in silicosis mouse lungs
Ramatroban reduces lung fibrosis induced by silica
Ramatroban reduces inflammation and improves pulmonary function
PGD2 and TXA2 were significantly increased in silicosis mouse lungs
Ramatroban reduces inflammation and improves pulmonary function
Ramatroban reduces inflammation and improves pulmonary function
Ramatroban reduces inflammation and improves pulmonary function
Ra=ramatroban; Crs=compliance of the respiratory system
Ramatroban improves cardiopulmonary function
Ramatroban reduces inflammation and improves pulmonary function
Ramatroban reduces inflammation and improves pulmonary function
RVSP=right ventricular systolic pressure; RVHI= right ventricular hypertrophy index