TY - JOUR
T1 - Fibrodysplasia ossificans progressiva
T2 - A blueprint for metamorphosis
AU - Kaplan, Frederick S.
AU - Lounev, Vitali Y.
AU - Wang, Haitao
AU - Pignolo, Robert J.
AU - Shore, Eileen M.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2011/11
Y1 - 2011/11
N2 - The most important milestone in understanding a genetic disease is the identification of the causative mutation. However, such knowledge is often insufficient to decipher the pathophysiology of the disorder or to effectively treat those affected. Fibrodysplasia ossificans progressiva (FOP) is a rare, disabling, genetic disease of progressive heterotopic endochondral ossification (HEO) enabled by missense mutations that promiscuously and provisionally activate ACVR1/ALK2, a bone morphogenetic protein (BMP) type I receptor, in all affected individuals. While activating mutations of the ACVR1/ALK2 receptor are necessary, disease activity and progression also depend on altered cell and tissue physiology. Recent findings identify inflammatory and immunological factors, vascular-derived mesenchymal stem cells, and a hypoxic lesional microenvironment that trigger, promote, and enable episodic progression of FOP in the setting of the genetic mutation. Effective therapies for FOP will need to consider these seminal pathophysiologic interactions.
AB - The most important milestone in understanding a genetic disease is the identification of the causative mutation. However, such knowledge is often insufficient to decipher the pathophysiology of the disorder or to effectively treat those affected. Fibrodysplasia ossificans progressiva (FOP) is a rare, disabling, genetic disease of progressive heterotopic endochondral ossification (HEO) enabled by missense mutations that promiscuously and provisionally activate ACVR1/ALK2, a bone morphogenetic protein (BMP) type I receptor, in all affected individuals. While activating mutations of the ACVR1/ALK2 receptor are necessary, disease activity and progression also depend on altered cell and tissue physiology. Recent findings identify inflammatory and immunological factors, vascular-derived mesenchymal stem cells, and a hypoxic lesional microenvironment that trigger, promote, and enable episodic progression of FOP in the setting of the genetic mutation. Effective therapies for FOP will need to consider these seminal pathophysiologic interactions.
KW - ACVR1
KW - ALK2
KW - BMP
KW - Fibrodysplasia
KW - Heterotopic ossification
KW - Ossificans progressiva
UR - http://www.scopus.com/inward/record.url?scp=81255197446&partnerID=8YFLogxK
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U2 - 10.1111/j.1749-6632.2011.06195.x
DO - 10.1111/j.1749-6632.2011.06195.x
M3 - Article
C2 - 22082359
AN - SCOPUS:81255197446
VL - 1237
SP - 5
EP - 10
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
SN - 0077-8923
IS - 1
ER -