A charitable donation will sponsor two new postdoctoral scientists for research into the rare bone disease fibrodysplasia ossificans progressiva (FOP) led by Dr Alex Bullock of the Structural Genomics Consortium (SGC) and Professor James Triffitt of the Botnar Research Centre. The funding available for three years will establish a dedicated programme to study the gene responsible for FOP and how drugs can be developed to halt or prevent this disabling condition.
The donation comes from Mr Richard Simcox, via his company Roemex Ltd, who is President of the FOP patients group ‘FOP Action UK’. FOP, also known as Stone Man Syndrome, is a progressive disease in which new bone forms in muscles, ligaments and tendons, often as a result of inflammation following injury or trauma. Patients become immobilised in mid-life as the joints are locked in place by new bone tissue. It is a very rare condition with no known cure - any surgery would only exacerbate the condition.
In 2006, Professor Triffitt and colleagues at Oxford were part of an international collaboration that identified the gene responsible for FOP, working with families who had the disease in the UK. The identified gene ACVR1 encodes for a receptor protein kinase that binds growth factors for bone formation (BMPs). In FOP patients, a mutation in this gene activates the receptor triggering bone formation during episodes of inflammation.
Since the gene was first identified, there has been significant research progress. Researchers in the US were able to show that a chemical inhibitor of ACVR1 could limit the development of extraskeletal bone in a mouse model for FOP. Dr Alex Bullock and colleagues at the SGC were able to solve the structure of ACVR1 to show how this inhibitor class worked, providing a lead for further structure-based drug design.
The two new researchers at Oxford will start projects to further understand the structure of the mutant protein, how drugs can be best designed to stop its action, and to carry out the cell biology necessary to test whether any new, early-stage drug candidates are working in the right way. The project is highlighted as a milestone in University of Oxford's fundraising campaign, Oxford Thinking.