Researchers discover possible cause of ‘Stone Man Syndrome’

A team of geneticists believe they may have discovered the reason that people suffering from an unusual condition known as fibrodysplasia ossificans progressiva (FOP) see their muscles turn to bone, and the breakthrough could lead to a cure for the so-called “Stone Man Syndrome”.
According to Science, Aris Economides, a functional geneticist who heads up the skeletal disease program at Regeneron Pharmaceuticals in New York discovered that the painful process happens when a defective gene causes abnormal behavior in some parts of the cell membrane, causing the body’s soft tissue to occasionally and abruptly transform into unneeded bones.
Economides and his colleagues, who published their findings in the latest edition of the journal Science Transitional Medicine, found that the genetic mutation is shared by 97 percent of those with FOP, and as it so happened, the geneticist happened to have a treatment for this previously undiscovered molecular target sitting in a freezer in his laboratory.
Regeneron tested that potential therapy, a type of protein known as a monoclonal antibody, on mice suffering their own version of Stone Man Syndrome. They found that the rodent stopped growing unwanted new bones, and while it remains uncertain that the antibody will be effective on humans, the company is continuing to test it in the hopes of conducting clinical trials.
Unclear if the treatment will be effective on humans
FOP affects approximately two million people worldwide, according to the Huffington Post, and since it can change tissues and ligaments into bone anywhere in a person’s body, it can make the simplest of tasks (such as eating or breathing) exceptionally difficult. Stopping interactions at the cell membrane could provide new hope for treatment for this debilitating disease.
The genetic defect behind Stone Man Syndrome, a mutated version of the gene ACVR1 in which patients produce an overactive form on cell surface protein called a transmembrane receptor, was first discovered in 2006, Science explained. Normally, it responds to a partner molecule called a ligand by sending signals into cells to encourage bone growth.
Six years later, Economides and his colleagues at Regeneron attempted to find out exactly how the defective gene caused such excessive bone growth in FOP. They found that ligands were needed for excess bone to form. through blocking the ligand-receptor interaction in mice. Since there are multiple possible ligands, and not all of them could be blocked in humans, however, they had to find the right one.
They ultimately found that activins, a type of ligand that had not previously been linked to FOP, were responsible for activating the mutant form of ACVR1. Their findings, combined with work conducted at the University of Pennsylvania, ultimately revealed that activin A works differently in people with FOP. While it inhibits ACVR1 receptor activation in healthy people, it spurs bone growth in people with Stone Man Syndrome, according to the study authors.
Using an antibody blocking activin A that was stored in Regeneron’s freezer, the research team was able to prevent an FOP-like disease in mice. However, Frederick Kaplan, of the Penn study, cautioned that it is not clear what the significance of this will be for humans. He added that his team is attempting to verify the findings in both FOP patients and health men and women.
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