Office of Technology Transfer – University of Michigan

Prevention and Treatment of Traumatic Heterotopic Ossification and Fibrodysplasia Ossificans Progressiva

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Benjamin Levi
Managed By
Ed Pagani
Associate Director, Health Technologies 734-763-3558
Patent Protection
US Patent Pending
US Patent Pending
Inhibition of Hif1α prevents both trauma-induced and genetic heterotopic ossification
Proceedings of the National Academy of Sciences of the United States of America. vol. 113 no. 3 Shailesh Agarwal,  E338–E347, doi: 10.1073/pnas.1515397113, 2015

Heterotopic ossification (HO) is a severely debilitating formation of abnormal bone growth resulting from trauma-induced injury to musculoskeletal and central nervous systems, including major burns and orthopedic interventions. Estimated to complicate up to 80% of hip replacements and 20% of spinal cord injuries in the civilian population, HO also affects more than 60% of military personnel with combat-induced wounds. A rare genetic disorder causing a mutation in the ACVR1 gene, fibrodysplasia ossificans progressiva is another cause of HO in areas of soft tissue damage resulting in severe restrictions in motion. Radiographic diagnosis of the disease is difficult, and a lack of effective treatments for trauma-induced HO limit options to invasive surgery, but even surgical resection of bone can result in its recurrence. There is a major clinical need for the prevention and treatment of both the acquired and congenital forms of this disease.

Prevention and Treatment of Trauma-Induced and Genetic Heterotopic Ossification

Recent studies identify pharmacologic inhibitors of ectopic bone formation that can be used for prevention and treatment applicable to both forms of HO. Data acquired using animal models with trauma-induced and genetic variations of HO identify a common target for the inhibition of extraskeletal bone formation. Prevention of HO or its elimination is achieved at burn/tenotomy sites and non-trauma models of genetically-induced ossification resulting from the ACVR1 gene mutation. Results show greater efficiency of inhibiting ossification over other known inhibitors of bone morphogenetic protein (BMP), a group of growth factors known to regulate bone formation.


  • New target for treatment and prevention of heterotopic ossification after trauma, burn injuries
  • Post-surgical prevention of ossification in patients with hip replacements, spinal surgery
  • Treatment of fibrodysplasia ossificans progressiva


  • Therapeutics with existing use in treatment of human medical conditions
  • Treatment targets both genetic and non-genetic HO disease forms