For patients with a rare genetic disorder that turns their muscles into bone, there is new hope. The disease is called fibrodysplasia ossificans progressiva (FOP), or “stone man syndrome.”
It gradually replaces muscle, tendons, ligaments, and other soft tissue with bone, essentially causing the body to grow a second skeleton.
It is an extremely rare disease that is estimated to affect around one in one million people. FOP is caused by a mutation in a gene known as ACVR1, which is involved in a cellular process that regulates the skeleton’s development in the womb and repairs the skeleton throughout life.
The mutation makes the ACVR1 gene more active, leading to bone formation that is unnecessary. In most cases, the mutation randomly occurs in people who don’t have any family history of the disease.
One of the first signs of FOP is that a person will have shortened and turned-in big toes from birth. Around 50 percent of patients will also have malformed thumbs.
Symptoms of FOP usually start during childhood. Some of the earliest affected areas are the neck, back, chest, arms, and legs.
They may experience difficulty with speaking or eating, hearing loss, and spinal deformity. By the age of 30, most patients with FOP cannot move at all.
The most common cause of death is cardiorespiratory failure due to patients not being able to breathe. On average, the life expectancy for individuals with this disease is about 56 years.
Researchers from Regeneron Pharmaceuticals working with mice have developed an antibody that blocks the activin A protein from triggering the ACVR1 gene.
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In lab mice that were genetically altered to carry the disease mutation, the antibody was successful in inhibiting bone formation. The results of the study provide hope for FOP patients.
“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, the director of global research development for the International FOP Association.
According to the International FOP Association, there are 800 confirmed cases across the globe, with 285 of them in the United States.
However, it is likely there are more cases of the diseases that have not yet been located. Until now, the only treatment for FOP has been the steroid drug prednisone, which helps manage pain.
“It’s not proven to do anything. It just helps them feel better through the pain of a flare-up,” Bogard said. “There’s nothing else that people can do. This disease is on a march through their bodies, and it’s not going to stop.”
Doctors cannot perform surgery to remove excess bone tissue because of the risk of triggering further flare-ups.
The recently developed antibody arrested bone formation in lab mice for up to six weeks. There were also no obvious side effects.
It is unclear when the antibody will be ready for testing in humans. Currently, Regeneron is conducting preclinical safety tests.
The study was published in Science Translational Medicine.
