From mysteries to medicines: drug development for fibrodysplasia ossificans progressive
Identifieur interne : 003625 ( Main/Exploration ); précédent : 003624; suivant : 003626From mysteries to medicines: drug development for fibrodysplasia ossificans progressive
Auteurs : Frederick S. Kaplan [États-Unis] ; Robert J. Pignolo [États-Unis] ; Eileen M. Shore [États-Unis]Source :
- Expert opinion on orphan drugs [ 2167-8707 ] ; 2013.
Abstract
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.
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.
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.
Url:
DOI: 10.1517/21678707.2013.825208
PubMed: 24800180
PubMed Central: 4007356
Affiliations:
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Kaplan</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Orthopaedic Surgery, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Orthopaedic Surgery, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Medicine, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Medicine, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A4">The Center for Research In FOP and Related Disorders; The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>The Center for Research In FOP and Related Disorders; The Perelman School of Medicine at The University of Pennsylvania, Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Pignolo, Robert J" sort="Pignolo, Robert J" uniqKey="Pignolo R" first="Robert J." last="Pignolo">Robert J. Pignolo</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Orthopaedic Surgery, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Orthopaedic Surgery, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Medicine, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Medicine, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A4">The Center for Research In FOP and Related Disorders; The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>The Center for Research In FOP and Related Disorders; The Perelman School of Medicine at The University of Pennsylvania, Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Shore, Eileen M" sort="Shore, Eileen M" uniqKey="Shore E" first="Eileen M." last="Shore">Eileen M. Shore</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Orthopaedic Surgery, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Orthopaedic Surgery, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A3">Department of Genetics, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Genetics, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A4">The Center for Research In FOP and Related Disorders; The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>The Center for Research In FOP and Related Disorders; The Perelman School of Medicine at The University of Pennsylvania, Philadelphia</wicri:cityArea></affiliation></author></analytic><series><title level="j">Expert opinion on orphan drugs</title><idno type="eISSN">2167-8707</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Introduction:</title><p id="P1">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.</p></sec><sec id="S2"><title>Areas covered:</title><p id="P2">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.</p></sec><sec id="S3"><title>Expert opinion:</title><p id="P3">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.</p></sec></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Pennsylvanie</li></region></list><tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Kaplan, Frederick S" sort="Kaplan, Frederick S" uniqKey="Kaplan F" first="Frederick S." last="Kaplan">Frederick S. Kaplan</name></region><name sortKey="Kaplan, Frederick S" sort="Kaplan, Frederick S" uniqKey="Kaplan F" first="Frederick S." last="Kaplan">Frederick S. Kaplan</name><name sortKey="Kaplan, Frederick S" sort="Kaplan, Frederick S" uniqKey="Kaplan F" first="Frederick S." last="Kaplan">Frederick S. Kaplan</name><name sortKey="Pignolo, Robert J" sort="Pignolo, Robert J" uniqKey="Pignolo R" first="Robert J." last="Pignolo">Robert J. Pignolo</name><name sortKey="Pignolo, Robert J" sort="Pignolo, Robert J" uniqKey="Pignolo R" first="Robert J." last="Pignolo">Robert J. Pignolo</name><name sortKey="Pignolo, Robert J" sort="Pignolo, Robert J" uniqKey="Pignolo R" first="Robert J." last="Pignolo">Robert J. Pignolo</name><name sortKey="Shore, Eileen M" sort="Shore, Eileen M" uniqKey="Shore E" first="Eileen M." last="Shore">Eileen M. Shore</name><name sortKey="Shore, Eileen M" sort="Shore, Eileen M" uniqKey="Shore E" first="Eileen M." last="Shore">Eileen M. Shore</name><name sortKey="Shore, Eileen M" sort="Shore, Eileen M" uniqKey="Shore E" first="Eileen M." last="Shore">Eileen M. Shore</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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