Strategic Targeting of Multiple BMP Receptors Prevents Trauma-Induced Heterotopic Ossification

Trauma-caused heterotopic ossification (tHO) is really a condition of pathologic wound healing, based on the progressive formation of ectopic bone in soft tissue following severe burns or trauma. Because previous research has proven that genetic variants of HO, for example fibrodysplasia ossificans progressiva (FOP), come from hyperactivating mutations from the type I bone morphogenetic protein receptor (T1-BMPR) ACVR1/ALK2, studies evaluating therapies for HO happen to be directed mainly toward drugs with this specific receptor. However, patients with tHO don’t carry known T1-BMPR mutations. Ideas reveal that, although BMP signaling is needed for tHO, not one T1-BMPR (ACVR1/ALK2, BMPR1a/ALK3, or BMPR1b/ALK6) alone is essential with this disease, suggesting these receptors have functional redundancy within the setting of tHO. Through the use of two different classes of BMP signaling inhibitors, we created a translational method of treatment, integrating treatment choice with existing diagnostic options. Our treatment paradigm balances either immediate therapy with reduced risk for negative effects (Alk3-Fc) or delayed therapy with improved patient selection but and the higher chances for negative effects (LDN-212854).