TY - JOUR
T1 - From mysteries to medicines
T2 - Drug development for fibrodysplasia ossificans progressiva
AU - Kaplan, Frederick S.
AU - Pignolo, Robert J.
AU - Shore, Eileen M.
N1 - Funding Information:
This work was supported in part by the International Fibro-dysplasia Ossificans Progressiva (FOP) Association, The Center for Research in FOP & Related Disorders, the Ian Cali Endowment for FOP Research, The Whitney Weldon Endowment for FOP Research, The Isaac & Rose Nassau Professorship of Orthopaedic Molecular Medicine (to FSK), The Cali-Weldon Professorship for FOP Research (to EMS), and by grants from the Rita Allen Foundation, and the US National Institutes of Health (NIH R01 AR04196). The authors have no further competing interests to declare.
PY - 2013
Y1 - 2013
N2 - Introduction: Fibrodysplasia ossificans progressiva (FOP) is the most disabling disorder of skeletal metamorphosis in humans and leads to the formation of a second skeleton of heterotopic bone. Presently, there is no effective treatment. Areas covered: In this review, the authors discuss heterozygous activating mutations in Activin receptor A, type I/activin-like kinase 2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor that are the genetic cause of FOP and reveal a promising pharmacologic target in the BMP signaling pathway. Despite these germline mutations, episodic disease activation is induced by soft tissue injury and resultant inflammatory triggers that are dependent on responding progenitor cells and a tissue microenvironment that supports heterotopic ossification. Expert opinion: Here, we review opportunities and challenges for the development of effective therapeutics for FOP. There are many potential approaches that may eventually be used to harness FOP. The long-term treatment of FOP is likely to involve not one, but several concomitant approaches that acknowledge molecular mechanisms involved in the induction and progression of the disease.
AB - Introduction: Fibrodysplasia ossificans progressiva (FOP) is the most disabling disorder of skeletal metamorphosis in humans and leads to the formation of a second skeleton of heterotopic bone. Presently, there is no effective treatment. Areas covered: In this review, the authors discuss heterozygous activating mutations in Activin receptor A, type I/activin-like kinase 2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor that are the genetic cause of FOP and reveal a promising pharmacologic target in the BMP signaling pathway. Despite these germline mutations, episodic disease activation is induced by soft tissue injury and resultant inflammatory triggers that are dependent on responding progenitor cells and a tissue microenvironment that supports heterotopic ossification. Expert opinion: Here, we review opportunities and challenges for the development of effective therapeutics for FOP. There are many potential approaches that may eventually be used to harness FOP. The long-term treatment of FOP is likely to involve not one, but several concomitant approaches that acknowledge molecular mechanisms involved in the induction and progression of the disease.
KW - Bone morphogenetic protein receptors
KW - Fibrodysplasia ossificans progressiva
KW - Heterotopic endochondral ossification
KW - Skeletal metamorphosis
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U2 - 10.1517/21678707.2013.825208
DO - 10.1517/21678707.2013.825208
M3 - Review article
AN - SCOPUS:84896710829
SN - 2167-8707
VL - 1
SP - 637
EP - 649
JO - Expert Opinion on Orphan Drugs
JF - Expert Opinion on Orphan Drugs
IS - 8
ER -