Inflammation is a key step in the progression of heterotopic ossification ? where soft tissue turns into bone ? according to research in Nature Medicine this week. The study shows that an inhibitor of the disease gene’s protein product is partially therapeutic, and therefore offers hope for this devastating condition.
In a reverse of the ancient myth of Pygmalion, where a statue comes to life, sufferers of heterotopic ossification have their fibrous tissue ‘ossified’ ? in effect, turning the patients into statues. A major form of heterotopic ossification is fibrodysplasia ossificans progressiva (FOP), which in about 98% of cases results from a mutation in a specific bone morphogenetic protein receptor.
A mouse model of FOP involving the same mutation found in people has yet to be made, but Paul Yu and colleagues have now developed a mouse model of the general phenomenon by expressing a related version of the mutated receptor. They found that just expressing the mutant version of the protein receptor was not sufficient to cause the disease ? an inflammatory stimulus was also needed. Yu’s team also show that inhibiting inflammation with glucocorticoids?a treatment commonly used in the clinic?helps reduce the incidence of heterotopic ossification in their model.
Importantly, the authors also show that a small molecule inhibitor of the protein receptor likewise reduced the incidence of disease progression. This form of treatment represents a potential breakthrough, as long-term use of glucocorticoids causes severe side-effects. The authors caution, however, that much more research is needed before the drug could be considered for human trials.