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Heterotopic Ossification in Combat Amputees, Hip Replacement Patients, Head Injury Victims, Heart Valve Replacement Patients,and a New Jersey Governor

FOP may be the tip of an iceberg of conditions in
which individuals form heterotopic bone. Drs. Robert Pignolo,
Mary Ann Keenan, and colleagues from The University of
Pennsylvania are investigating the role of ACVR1 in non-
hereditary forms of heterotopic ossification that plague millions
of individuals worldwide including athletes, amputees, hip
replacement patients, head injury victims, patients who have
endstage valvular heart disease, and even a New Jersey
governor who sustained severe bone and soft tissue injuries
in an automobile accident and who subsequently developed
massive heterotopic bone.

While specific mutations in ACVR1 have not been found in
patient population, the ACVR1 receptor and downstream BMP
signaling pathway are highly likely to be involved in these
non-hereditary forms of heterotopic ossification. If pharmaceutical
companies are to derive an economic benefit in developing
drugs that block the formation of heterotopic bone in FOP,
it will be in this very large and diverse patient population
who have more common forms of heterotopic ossification and
whose bodies are likely to use the same molecular blueprints
(as in FOP) in forming their extra and unwanted bones. We
will keep you informed aboutthis exciting new area of
investigation in future reports.

Drs. Shore, Pignolo and Kaplan meet with Dr. Charles
Hong, M.D., Ph.D., from Vanderbilt University
(second from right) at the FOP Laboratory in Philadelphia