| Project 11 |
|
Preventing ectopic bone formation in a model of Fibrodysplasia Ossificans Progressiva (FOP)Prof. Seemann (first supervisor), Prof. Schomburg (second supervisor); Charité Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic condition that leads to ectopic bone formation in soft tissues thereby building a second skeleton which limits the patient's mobility progressively during lifetime. Since 2006 it is known that a mutation in a Bone Morphogenetic Protein receptor (ACVR1) causes FOP. The ectopic bone formation occurs sporadically and is often induced by trauma or by inflammation. We were able to show that NOGGIN, a well known BMP antagonist, is not able to block the activity of the receptor carrying the FOP mutation. Therefore, this project aims to characterize ectopic bone formation caused by FOP mutations on a molecular level and to identify inhibitors to prevent this process. The spectrum of methods will be cell culturing, molecular biology and in vivo models. We expect to gain further insight into this rare disease and to assist in the generation of respective inhibitors which hopefully will find their way into the clinics for the benefit of the patients. Kaplan FS, Xu M, Seemann P, Connor JM, Glaser DL, Carroll L, Delai P, Fastnacht-Urban E, Forman SJ, Gillessen-Kaesbach G, Hoover-Fong J, Köster B, Pauli RM, Reardon W, Zaidi SA, Zasloff M, Morhart R, Mundlos S, Groppe J, Shore EM. Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Hum Mutat. 2009 Mar;30(3):379-90. Kaplan FS, Shen Q, Lounev V, Seemann P, Groppe J, Katagiri T, Pignolo RJ, Shore EM. Skeletal metamorphosis in fibrodysplasia ossificans progressiva (FOP). J Bone Miner Metab. 2008;26(6):521-30. Review. Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M, Morhart R, Rogers JG, Smith R, Triffitt JT, Urtizberea JA, Zasloff M, Brown MA, Kaplan FS. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet. 2006 May;38(5):525-7. Epub 2006 Apr 23. |
