From mysteries to medicines: drug development for fibrodysplasia ossificans progressive
Identifieur interne : 003612 ( Pmc/Curation ); précédent : 003611; suivant : 003613From 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
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :003613
Links to Exploration step
PMC:4007356Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">From mysteries to medicines: drug development for fibrodysplasia ossificans progressive</title>
<author><name sortKey="Kaplan, Frederick S" sort="Kaplan, Frederick S" uniqKey="Kaplan F" first="Frederick S." last="Kaplan">Frederick S. 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>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">24800180</idno>
<idno type="pmc">4007356</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007356</idno>
<idno type="RBID">PMC:4007356</idno>
<idno type="doi">10.1517/21678707.2013.825208</idno>
<date when="2013">2013</date>
<idno type="wicri:Area/Pmc/Corpus">003613</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003613</idno>
<idno type="wicri:Area/Pmc/Curation">003612</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">003612</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">From mysteries to medicines: drug development for fibrodysplasia ossificans progressive</title>
<author><name sortKey="Kaplan, Frederick S" sort="Kaplan, Frederick S" uniqKey="Kaplan F" first="Frederick S." last="Kaplan">Frederick S. 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>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101601398</journal-id>
<journal-id journal-id-type="pubmed-jr-id">42374</journal-id>
<journal-id journal-id-type="nlm-ta">Expert Opin Orphan Drugs</journal-id>
<journal-id journal-id-type="iso-abbrev">Expert Opin Orphan Drugs</journal-id>
<journal-title-group><journal-title>Expert opinion on orphan drugs</journal-title>
</journal-title-group>
<issn pub-type="epub">2167-8707</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">24800180</article-id>
<article-id pub-id-type="pmc">4007356</article-id>
<article-id pub-id-type="doi">10.1517/21678707.2013.825208</article-id>
<article-id pub-id-type="manuscript">NIHMS564018</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>From mysteries to medicines: drug development for fibrodysplasia ossificans progressive</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Kaplan</surname>
<given-names>Frederick S.</given-names>
</name>
<degrees>M.D.</degrees>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pignolo</surname>
<given-names>Robert J.</given-names>
</name>
<degrees>M.D., Ph.D.</degrees>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shore</surname>
<given-names>Eileen M.</given-names>
</name>
<degrees>Ph.D.</degrees>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Department of Orthopaedic Surgery, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104</aff>
<aff id="A2"><label>2</label>
Department of Medicine, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104</aff>
<aff id="A3"><label>3</label>
Department of Genetics, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104</aff>
<aff id="A4"><label>4</label>
The Center for Research In FOP and Related Disorders; The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104</aff>
<author-notes><corresp id="CR1">Correspondence to: Frederick S. Kaplan, M.D. Isaac & Rose Nassau Professor of Orthopaedic Molecular Medicine The Perelman School of Medicine at the University of Pennsylvania C/o The Department of Orthopaedic Surgery Hospital of the University of Pennsylvania Silverstein 2 3400 Spruce Street Philadelphia, PA 19104 Telephone: 215-349-8726 Fax: 215-349-5298 <email>frederick.kaplan@uphs.upenn.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>13</day>
<month>4</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub"><month>8</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>01</day>
<month>8</month>
<year>2014</year>
</pub-date>
<volume>1</volume>
<issue>8</issue>
<fpage>637</fpage>
<lpage>649</lpage>
<pmc-comment>elocation-id from pubmed: 10.1517/21678707.2013.825208</pmc-comment>
<abstract><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>
</abstract>
<kwd-group><kwd>Bone morphogenetic protein receptors</kwd>
<kwd>Fibrodysplasia ossificans progressiva</kwd>
<kwd>Heterotopic endochondral ossification</kwd>
<kwd>Skeletal metamorphosis</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 003612 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 003612 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= LymphedemaV1 |flux= Pmc |étape= Curation |type= RBID |clé= PMC:4007356 |texte= From mysteries to medicines: drug development for fibrodysplasia ossificans progressive }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:24800180" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \ | NlmPubMed2Wicri -a LymphedemaV1
![]() | This area was generated with Dilib version V0.6.31. | ![]() |