Which best describes the proposed mechanism of action of palovarotene in FOP?

The proposed mechanism of action of palovarotene in the treatment of Fibrodysplasia Ossificans Progressiva (FOP) is best described as a retinoic acid receptor (RAR)-γ agonist that inhibits chondrogenesis. In the context of FOP, which is characterized by the abnormal formation of bone in muscles and connective tissues, managing this condition requires targeting pathways that lead to abnormal bone growth.

Palovarotene works by activating the retinoic acid receptor gamma, which has a critical role in regulating gene expression during the development of bone and cartilage. By engaging this receptor, palovarotene helps to inhibit the processes that lead to chondrogenesis and, consequently, the formation of ectopic bone, thereby reducing the risk of further abnormal ossification in patients with FOP.

This understanding is important since other mechanisms, such as those involving tyrosine kinase inhibition or monoclonal antibodies, do not specifically address the unique genetic and molecular pathways involved in the pathophysiology of FOP as effectively as palovarotene does through its action on retinoic acid receptors. Additionally, mTOR kinase inhibitors target broader cell growth pathways that are not specific to the mechanisms underlying FOP, making palovar