Antibody Treats Rare Bone Disorder In Mice

No treatments currently exist for fibrodysplasia ossificans progressiva (FOP)—a rare disease in which a person’s soft tissues ossify, or turn to bone. The genetic mutation that most commonly causes FOP swaps an arginine for a histidine in a bone-producing protein receptor called ACVR1. This leads to receptor hyperactivity and, in turn, abnormal bone growth. Now, a team from Regeneron Pharmaceuticals, in Tarrytown, N.Y., and Brigham & Women’s Hospital, in Boston, has created a mouse model to study FOP. The team tested whether activin A—a protein the body produces when injured—promoted bone growth in FOP mice (Sci. Transl. Med. 2015, DOI: 10.1126/scitranslmed.aac4358). Researchers soaked collagen sponges either in activin A or the bone-producing protein BMP2 and implanted them in FOP and control mice. The BMP2 sponges caused ossification in all mice, but the activin A sponges did so only in FOP mice—indicating that activin A triggers the severe ossification seen in patients with FOP. The team created human monoclonal antibodies that target activin A. Untreated FOP mice developed ossifications in three weeks, but mice treated with the antibody did not show significant ossification six weeks into testing.