Some marble statues seem to have more life in them than they do stone. It would hardly be surprising to see Michael Angelo’s David or Milo’s Venus step down from their pedestal. Stone coming to life is fantasy. However life shackled like stone is not. Some people are struck by a terrible hereditary illness – known as fibrodysplasia ossificans progressiva or FOP – where the formation of a second skeleton gradually imprisons them. However, following a recent discovery, there may be hope for FOP victims to regain mobility.
In FOP, muscles, tendons and ligaments ossify progressively from an early age on, slowly confining patients in a bone cage until their limbs and articulations are paralysed. Other muscles however, such as the heart or the diaphragm, are not touched. The pathways underlying ossification are still only partially understood, yet recently a protein involved in the normal process of ossification was discovered: the ACVR1 receptor. ACVR1 is found in numerous tissues on a cell’s membrane and binds to protein factors which regulate bone synthesis. The receptor then relays information from the outside of a cell to the inside by way of phosphorylation.
What happens in FOP patients? ACVR1 is subjected to a change in one amino acid. It may seem trivial, yet one amino acid modification is enough to hinder ACVR1 in its interactions with other protein factors. As a result, the modified ACVR1 is in part responsible for the bone anarchy reminiscent of FOP.
Such a discovery is astonishing because of the extreme rareness of this hereditary disease. And, what is more, it was all the more exciting because to this day no treatment had been able to help patients to escape from their bone shackles. Even surgery has failed since any intervention simply accelerates the formation of new and more robust bone.
Bone is not inert; ossification is a subtle balance between synthesis and degradation, and ACVR1 could well be sitting on the hinge of both extremes. Researchers consequently see in ACVR1 a protein which can both accelerate and hinder bone formation. As a result, it could be an important target in the treatment of osteoporosis– or any other instance in which bone is lost, as can be the case in various kinds of trauma –where it could be used to increase bone synthesis.