Scientists help steer toward more promising approaches for FOP

By The Science Advisory Board staff writers

June 20, 2022 -- University of Connecticut and Alexion Pharmaceuticals researchers investigating a potential cure for fibrodysplasia ossificans progressiva (FOP) instead found a concerning surprise -- blocking the protein responsible for the disease with a monoclonal antibody made the abnormal bone growth worse in mice.

Researchers worked with an antibody discovered by Alexion that interferes with the specific cell-surface receptor involved in FOP called activin A receptor type 1 (ACVR1). Their hypothesis was that if they blocked ACVR1, the abnormal bone growth would stop. However, it exacerbated the problem.

"The unexpected result: injecting the antibody into FOP mice caused a dramatic increase in inappropriate bone formation," said David Goldhamer, professor of molecular and cell biology at the University of Connecticut.

While researchers at Regeneron Pharmaceuticals used different antibodies and a different strain of FOP mice, they got the same adverse result. Neither research teams know why the respective antibodies dramatically worsened the disease in mice.


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