Breakthrough in rare disease that causes growth of second skeleton

Scientists have developed a potential antibody treatment for the rare genetic disease fibrodysplasia ossificans progressiva (FOP), in which muscle and soft tissue gradually turn to bone.

The disease is known to be caused by mutations in the ACVR1 gene, which codes for a receptor protein that controls bone and muscle development. The mutations make this protein much more active than usual, resulting in the formation of extra bones. This process is accelerated even by very minor injuries in people with FOP, and this extra bony tissue slowly immobilises the body, causing problems with eating, breathing and mobility and eventually death.

Dr Sarah Hatsell and her colleagues at Regeneron found that the overactivity of the mutant receptor is caused by its altered response to the signalling molecule Activin-A — this molecule normally makes AVCR1 less active, but in FOP patients Activin-A increases the activity of the mutated ACVR1 receptor, driving bone growth.

This led Dr Hatsell's team to investigate whether blocking Activin-A from binding to the receptor protein could prevent the excessive bone growth seen in FOP patients. They injected an antibody that blocks Activin-A into mice that had been genetically engineered to have symptoms similar to FOP. After the mice were treated, their muscles did not turn into bone.

It is not yet known whether the treatment will work in humans with FOP. Regeneron is currently performing preclinical safety testing and may eventually conduct clinical trials if a safe clinical trial can be designed. Normal clinical trials may be impossible because people with FOP are so sensitive to injuries; even a simple injection can trigger bone overgrowth.

'We are very fortunate and grateful that not only did Regeneron make this basic science discovery, but that, as a biotechnology company with expertise in developing antibodies, they are in a position to act on it and answer the next questions about whether this could lead to a meaningful therapy,' said Betsy Bogard, director of global research development for the International FOP Association.