The year has seen some exciting breakthroughs in the search for new treatments for FOP. We’ve known for some time now that the underlying cause of FOP is a single faulty gene called ACVR1. This gene produces an overactive receptor protein which acts as a critical messenger for growth factors that stimulate bone formation. In FOP, the mouth of the receptor loses proper control and sends out too much signal that says ‘make more bone, make more bone, make more bone’. Fortunately, there are many ways researchers could try to correct this faulty activity and stop the unwanted bone formation.
The team in Oxford have been taking lessons from the decades of cancer research. Just like the bone in FOP, many tumours grow because of the excessive growth factor signals that are sent from the mutated receptors found on cancer cells. Big pharmaceutical companies have developed lots of drug molecules that bind to the mouths of these receptors (just like babies’ dummies) to block their messages. The team in Oxford searched through libraries of these drug molecules to see if any of them could also bind to the mouth of the FOP receptor. Excitingly, they discovered that one of these clinical molecules was extremely good at stopping the FOP signals too. This compound has advanced to late stage clinical trials for various human cancers. Encouragingly, it meets all the criteria the team have been striving to achieve: it is potent, selective, stable and safe to use.
Following the discovery of the compound, the team performed a number of additional experiments to validate the suitability of the compound for clinical trials in FOP. This has included collaborating with a colleague Dr. Yu in Boston to test it in FOP mice. After a nervous wait, the team were delighted to hear that the compound had successfully prevented the mice from developing the bone lesions typical of FOP. A hopeful and incredible discovery! The team are now preparing grant applications to the government to get funding to support a clinical trial in FOP late next year. Note, this is a different research path to the one being trialled by Clementia who are using an experimental drug called palovarotene that acts elsewhere to stop the path of building cartilage and bone.
The team look forward to very exciting times ahead and would like to take this opportunity to thank everyone for their generous, ongoing support.
FULL RESEARCH UPDATE AVAILABLE BELOW