Fibrodysplasia Ossificans Progressiva (FOP) is a pediatric, congenital, rare but extremely severe musculoskeletal disorder. FOP is characterized by formation of large amounts of bone at the expense of muscle and connective tissues (a process called Heterotopic Ossification or HO) at multiple sites throughout the body, causing major health problems and occasionally leading to premature death. Most FOP cases are due to a recurrent activating mutation in the bone morphogenetic protein receptor ALK2 that induces ectopic recruitment of progenitor cells, differentiation of these cells into cartilage, and then replacement of that cartilage with bone via endochondral ossification. At present there are no treatments or cures to prevent HO in the FOP patients. Surgery cannot be used because it actually triggers even greater and more severe HO, making the situation far worse for the patients. There is also a non-genetic form of HO that is milder, usually occurs in adults, and is triggered by physical trauma, burns or invasive surgeries. Because of the nature of such inciting factors, this non-genetic form of HO is particularly common amongst severely wounded soldiers. Pioneering work carried out by our Investigators over the past few years has shown that synthetic agonists for nuclear retinoid receptors block chondrogenic cell differentiation and in turn prevent HO in genetic and non-genetic animal models of the disease. One such agonist is the drug Palovarotene that had been previously tested for another unrelated condition in a Phase II trial. Our results with this and similar drugs were strong and clear enough to prompt the attention and interest of the pharmaceutical company Clementia. Together with us and our colleagues in the Department of Orthopaedic Surgery at the University of Pennsylvania, Clementia has recently launched a FDA-approved Phase II clinical trial on FOP patients. If effective, Palovarotene would represent the first preventive treatment for HO in FOP patients and may turn out to be as effective against HO occurring in our wounded soldiers or other patients. The studies have been, and continue to be, supported by the Department of Defense.