Fibrodysplasia ossificans progressiva (FOP) is a rare disease in which the muscles and connective tissues (e.g. tendons and ligaments) slowly turn into bone. There is no treatment; as the disease progresses, the build-up of bone material around the joints gradually limits patients’ mobility, and can also result in difficulties eating, speaking and even breathing.
The aim of STOPFOP is to see if a drug called AZD0530 could be used to treat FOP. FOP is caused by a mutation in a gene that codes for a protein called ALK2 kinase. Studies in the lab have shown that AZD0530 blocks the action of ALK2 kinase, and in mice, the drug successfully stopped the formation of bone material in the soft tissues and kept the mice’s limbs moving.
AZD0530, also known as saracatinib, has already been tested for safety in humans in healthy volunteers and as a treatment for certain cancers. Now, the STOPFOP team plans to run a clinical trial of AZD0530 in 16 adults with FOP to see if it reduces the formation of new bone. They will work with patients, FOP experts and regulatory authorities throughout the project.
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STOPFOP is trialling the cancer drug saracatinib, which has shown promise in treating people with fibrodyplasia ossificans progressiva (FOP), a rare and devastating disease in which muscles, tendons and ligaments slowly turn to bone. ###People with FOP gradually get ‘locked in’ their bodies, making it difficult to move and breathe. It’s caused by a mutation in a single gene, called ACVR1, which encodes for the protein kinase ALK2. The mutation causes ALK2 to become overactive, causing muscles and connective tissues turn into bone. There is no drug to treat this disease.
STOPFOP was launched to trial an experimental drug from AstraZeneca called saracatinib, originally developed as a cancer drug. The project team has shown that it blocks the activity of ALK2 kinase in mice, preventing ectopic bone formation and keeping the joints mobile. We know enough about the drug’s safety and efficacy thanks to trials in humans with cancer as well as healthy volunteers, so researchers are now proceeding to trial the drug on people suffering from FOP.
The drug is taken orally, as a once-daily dose. The first patient is now progressing through the STOPFOP study, with the randomised control trial period due to be completed within six months. Success will be measured on the ability of saracatinib to show less increase in bone formation outside the skeleton.
‘We hope to stop the formation of bone, which will hopefully preserve the movement they have,’ says Marelise Eekhoff of Amsterdam UMC, referring to the patients enrolled in the trial. ‘A 100% effect given the complexity of the clinical picture is almost impossible. We have given the definition of a success at least more than 50% reduction in bone formation outside the skeleton compared to controls. But in this disease even any effect would be useful.’
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ParticipantsShow participants on map
- Astrazeneca AB, Södertälje, Sweden
Universities, research organisations, public bodies, non-profit groups
- Brigham Inc, Boston, United States
- Klinikum Garmisch-Partenkirchen GMBH, Garmisch-Partenkirchen, Germany
- Stichting Vumc, Amsterdam, Netherlands
- The Royal National Orthopaedic Hospital National Health Service Trust, Stanmore, United Kingdom
- University of Oxford, Oxford, United Kingdom
|Name||IHI funding in €|
|Brigham Inc||1 875|
|Klinikum Garmisch-Partenkirchen GMBH||238 303|
|Stichting Vumc||568 239|
|The Royal National Orthopaedic Hospital National Health Service Trust||189 418|
|University of Oxford||1 875|
|Total Cost||999 710|