Conclusions and Proposals for Future Work

One area of FOP that would be important to study in more detail is the development of an inhibitor that attacks BMP signaling. One of the difficulties of this type of treatment is that we did not know exactly how to determine when a flare-up was beginning through certain biomarkers. Micha et al identified potential biomarkers present during cell differentiation to bone. In order to develop a treatment for FOP, there are two areas that need to be studied further. The exact mechanism of an FOP flare-up needs to be worked out in detail in order to identify the most promising drug targets. Knowing how the flare-ups progress would also assist us in identifying when exactly is the optimal time to treat the flare-up. Yu et al had developed a small molecule that had potential as a therapeutic inhibitor of Smad signaling. It would be beneficial to expand upon their study and determine whether it is possible to optimize the inhibitory effects of the molecule.

Exon skipping. Source:
Exon skipping. Source: Shi et al 2013

One research group studied a novel way to prevent ossification: knocking out increased ACVR1 activity by using exon skipping (Shi et al 2013). The potential therapeutic effects of this type of treatment are unknown because it has not been studied in an animal model of FOP (Shi et al 2013). Attempting to develop this type of treatment for a mouse model would help us to understand its effects on a living organism. What are the potential harms of knocking down ACVR1 activity? Does it have any therapeutic benefit? Another area that needs to be explored is the development of a reliable mouse model of FOP. Mice have been used in different ways, but there is a lack of universal mouse model.

Immune involvement in FOP. Source:
Immune involvement in FOP. Source: Gannon et al 2001

A final area that should be explored in further detail is the role of the immune response in FOP. The inflammatory response of the immune system has been shown to play a role in FOP, but the specifics are not yet known (Gannon et al 2001). It would be interesting to see what happens when certain inflammatory agents are inhibited. Does the inflammation cause the ossification? Or is it a result of the beginning stages of a flare-up? The lack of concrete knowledge of the flare-up mechanism is a hindrance to drug development. Exploring the role of inflammation provides more information on this puzzle and could lead to beneficial therapies in the future.