Inflammation is a key step in the progression of heterotopic ossification -- where soft tissue turns into bone -- according to research in Nature Medicine. 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 and Galatea, where a statue comes to life, sufferers of heterotopic ossification have their fibrous tissue 'ossified'. 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. Author contact: Paul B. Yu (Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA)
E-mail: pbyu@partners.org Abstract available online. (C) Nature Medicine press release.
Message posted by: Trevor M. D'Souza
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