Facing down Medusa

 作者:卢炻饷     |      日期:2019-03-08 03:04:05
By Andy Coghlan THE genetic roots of a rare disease that transfixes its victims as surely as the gaze of the mythical Medusa may soon be uncovered. As well as raising hopes for treating the condition, which gradually transforms muscle into bone, the discovery could revolutionise reconstructive plastic surgery and the repair of serious fractures. Fred Kaplan and his colleagues at the University of Pennsylvania in Philadelphia have now traced the inherited condition, known as fibrodysplasia ossificans progressiva or FOP, to small regions of chromosomes 2 and 4. Finding genetic markers for the disease is difficult because there are hardly any families with several generations of sufferers. “People are so incapacitated, they don’t have families,” explains Kaplan. This makes it hard to tease out genetic differences between healthy and affected relatives. Kaplan and his colleagues began to make progress after discovering four multigenerational families with the disease. Their progress could be even faster if they find more families with FOP to take part in the study. Their research has centred on a protein known as bone morphogenic protein-4 (BMP-4), which regulates skeletal formation in the embryo and plays a pivotal role in healing fractures. Two years ago, Kaplan’s team discovered that white blood cells in children with FOP contain abnormally high concentrations of BMP-4. Kaplan now believes that the white blood cells begin the process of turning soft tissue into bone by clumping around joints and making the smooth muscle cells lining nearby blood vessels become fibrous. It appears that these rogue muscle cells promote the painful and disfiguring transformation of neighbouring muscle, tendons and ligaments into bone. According to Kaplan, the disease is likely to be caused by a defective “master gene” that orchestrates the production of BMP-4. Once the gene is found, drugs could be developed to block its action and bring relief to FOP sufferers, whose joints are gradually locked in place by the condition. By activating the gene in cultured muscle cells, it may also become possible to grow bone prostheses. Plastic surgeons could use them to reconstruct the faces of accident victims, for instance. “The root cause of this disease is relevant to every condition that affects the formation of the skeleton,” says Kaplan, who presented his findings last week at a conference on bone growth in Zagreb,