RKER-012, a novel activin receptor type II ligand trap, protects against bone loss induced by pulmonary arterial hypertension (PAH) in a rat model of the disease. This is according to results from a preclinical study presented at the American Society for Bone and Mineral Research (ASBMR) 2021 Annual Meeting.

“We are excited to announce additional preclinical data from our KER-012 program,” Jasbir S. Seehra, PhD, president and chief executive officer of Keros Therapeutics, the developer of RKER-012, said in a press release. ”The results of this study suggest that RKER-012 prevented bone loss in this PAH model, which we believe supports that KER-012 has the potential to treat bone loss resulting from secondary osteoporosis, such as in PAH.”

KER-012 binds to transforming growth factor-beta ligands that suppress bone growth such as activin A and activin B, thereby inhibiting their action. According to the company, KER-012 could increase the signaling of bone morphogenic protein (BMP) pathways by inhibiting activin A and activin B signaling. This could help treat PAH where BMP signaling is reduced due to mutations in the genes that encode for BMP receptors, making them inactive.


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During the preclinical study, PAH rats subjected to chronic hypoxia were treated with either 20 mg/kg of RKER-012 or a vehicle twice a week for 4 weeks. Rats that were maintained under normal oxygen conditions only received the vehicle. 

The results showed that PAH rats maintained under hypoxic conditions and treated with vehicle had reduced bone volume, lower bone volume fraction, reduced trabecular number, and increased trabecular separation compared to rats maintained under normal oxygen conditions. 

However, when PAH rats maintained under hypoxic conditions were treated with RKER-012, their bone volume and trabecular number increased, they had higher bone volume fraction, and their trabecular separation decreased. These parameters were equivalent to control animals kept under normal oxygen conditions, suggesting that RKER-012 protected rats from PAH-induced bone loss.

Reference

Keros Therapeutics presents results from a preclinical study of RKER-012 in pulmonary arterial hypertension-associated bone loss at the American Society for Bone and Mineral Research 2021 Annual Meeting. News release. Keros Therapeutics; October 4, 2021.