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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Targeting Chelatable Iron as a Therapeutic Modality in Parkinson's Disease</title><author><name sortKey="Devos, David" sort="Devos, David" uniqKey="Devos D" first="David" last="Devos">David Devos</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Moreau, Caroline" sort="Moreau, Caroline" uniqKey="Moreau C" first="Caroline" last="Moreau">Caroline Moreau</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Devedjian, Jean Christophe" sort="Devedjian, Jean Christophe" uniqKey="Devedjian J" first="Jean Christophe" last="Devedjian">Jean Christophe Devedjian</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Kluza, Jerome" sort="Kluza, Jerome" uniqKey="Kluza J" first="Jérome" last="Kluza">Jérome Kluza</name><affiliation><nlm:aff id="aff5"></nlm:aff></affiliation></author><author><name sortKey="Petrault, Maud" sort="Petrault, Maud" uniqKey="Petrault M" first="Maud" last="Petrault">Maud Petrault</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Laloux, Charlotte" sort="Laloux, Charlotte" uniqKey="Laloux C" first="Charlotte" last="Laloux">Charlotte Laloux</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Jonneaux, Aurelie" sort="Jonneaux, Aurelie" uniqKey="Jonneaux A" first="Aurélie" last="Jonneaux">Aurélie Jonneaux</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Ryckewaert, Gilles" sort="Ryckewaert, Gilles" uniqKey="Ryckewaert G" first="Gilles" last="Ryckewaert">Gilles Ryckewaert</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Garcon, Guillaume" sort="Garcon, Guillaume" uniqKey="Garcon G" first="Guillaume" last="Garçon">Guillaume Garçon</name><affiliation><nlm:aff id="aff6"></nlm:aff></affiliation></author><author><name sortKey="Rouaix, Nathalie" sort="Rouaix, Nathalie" uniqKey="Rouaix N" first="Nathalie" last="Rouaix">Nathalie Rouaix</name><affiliation><nlm:aff id="aff7"></nlm:aff></affiliation></author><author><name sortKey="Duhamel, Alain" sort="Duhamel, Alain" uniqKey="Duhamel A" first="Alain" last="Duhamel">Alain Duhamel</name><affiliation><nlm:aff id="aff8"></nlm:aff></affiliation></author><author><name sortKey="Jissendi, Patrice" sort="Jissendi, Patrice" uniqKey="Jissendi P" first="Patrice" last="Jissendi">Patrice Jissendi</name><affiliation><nlm:aff id="aff9"></nlm:aff></affiliation></author><author><name sortKey="Dujardin, Kathy" sort="Dujardin, Kathy" uniqKey="Dujardin K" first="Kathy" last="Dujardin">Kathy Dujardin</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Auger, Florent" sort="Auger, Florent" uniqKey="Auger F" first="Florent" last="Auger">Florent Auger</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation><affiliation><nlm:aff id="aff10"></nlm:aff></affiliation></author><author><name sortKey="Ravasi, Laura" sort="Ravasi, Laura" uniqKey="Ravasi L" first="Laura" last="Ravasi">Laura Ravasi</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation><affiliation><nlm:aff id="aff11"></nlm:aff></affiliation></author><author><name sortKey="Hopes, Lucie" sort="Hopes, Lucie" uniqKey="Hopes L" first="Lucie" last="Hopes">Lucie Hopes</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Grolez, Guillaume" sort="Grolez, Guillaume" uniqKey="Grolez G" first="Guillaume" last="Grolez">Guillaume Grolez</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Firdaus, Wance" sort="Firdaus, Wance" uniqKey="Firdaus W" first="Wance" last="Firdaus">Wance Firdaus</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Sablonniere, Bernard" sort="Sablonniere, Bernard" uniqKey="Sablonniere B" first="Bernard" last="Sablonnière">Bernard Sablonnière</name><affiliation><nlm:aff id="aff7"></nlm:aff></affiliation></author><author><name sortKey="Strubi Vuillaume, Isabelle" sort="Strubi Vuillaume, Isabelle" uniqKey="Strubi Vuillaume I" first="Isabelle" last="Strubi-Vuillaume">Isabelle Strubi-Vuillaume</name><affiliation><nlm:aff id="aff7"></nlm:aff></affiliation></author><author><name sortKey="Zahr, Noel" sort="Zahr, Noel" uniqKey="Zahr N" first="Noel" last="Zahr">Noel Zahr</name><affiliation><nlm:aff id="aff12"></nlm:aff></affiliation></author><author><name sortKey="Destee, Alain" sort="Destee, Alain" uniqKey="Destee A" first="Alain" last="Destée">Alain Destée</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff13"></nlm:aff></affiliation></author><author><name sortKey="Corvol, Jean Christophe" sort="Corvol, Jean Christophe" uniqKey="Corvol J" first="Jean-Christophe" last="Corvol">Jean-Christophe Corvol</name><affiliation><nlm:aff id="aff14"></nlm:aff></affiliation></author><author><name sortKey="Poltl, Dominik" sort="Poltl, Dominik" uniqKey="Poltl D" first="Dominik" last="Pöltl">Dominik Pöltl</name><affiliation><nlm:aff id="aff15"></nlm:aff></affiliation><affiliation><nlm:aff id="aff16"></nlm:aff></affiliation></author><author><name sortKey="Leist, Marcel" sort="Leist, Marcel" uniqKey="Leist M" first="Marcel" last="Leist">Marcel Leist</name><affiliation><nlm:aff id="aff15"></nlm:aff></affiliation><affiliation><nlm:aff id="aff16"></nlm:aff></affiliation></author><author><name sortKey="Rose, Christian" sort="Rose, Christian" uniqKey="Rose C" first="Christian" last="Rose">Christian Rose</name><affiliation><nlm:aff id="aff17"></nlm:aff></affiliation></author><author><name sortKey="Defebvre, Luc" sort="Defebvre, Luc" uniqKey="Defebvre L" first="Luc" last="Defebvre">Luc Defebvre</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Marchetti, Philippe" sort="Marchetti, Philippe" uniqKey="Marchetti P" first="Philippe" last="Marchetti">Philippe Marchetti</name><affiliation><nlm:aff id="aff5"></nlm:aff></affiliation></author><author><name sortKey="Cabantchik, Z Ioav" sort="Cabantchik, Z Ioav" uniqKey="Cabantchik Z" first="Z. Ioav" last="Cabantchik">Z. Ioav Cabantchik</name><affiliation><nlm:aff id="aff18"></nlm:aff></affiliation></author><author><name sortKey="Bordet, Regis" sort="Bordet, Regis" uniqKey="Bordet R" first="Régis" last="Bordet">Régis Bordet</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24251381</idno><idno type="pmc">4060813</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060813</idno><idno type="RBID">PMC:4060813</idno><idno type="doi">10.1089/ars.2013.5593</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000425</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000425</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Targeting Chelatable Iron as a Therapeutic Modality in Parkinson's Disease</title><author><name sortKey="Devos, David" sort="Devos, David" uniqKey="Devos D" first="David" last="Devos">David Devos</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Moreau, Caroline" sort="Moreau, Caroline" uniqKey="Moreau C" first="Caroline" last="Moreau">Caroline Moreau</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Devedjian, Jean Christophe" sort="Devedjian, Jean Christophe" uniqKey="Devedjian J" first="Jean Christophe" last="Devedjian">Jean Christophe Devedjian</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Kluza, Jerome" sort="Kluza, Jerome" uniqKey="Kluza J" first="Jérome" last="Kluza">Jérome Kluza</name><affiliation><nlm:aff id="aff5"></nlm:aff></affiliation></author><author><name sortKey="Petrault, Maud" sort="Petrault, Maud" uniqKey="Petrault M" first="Maud" last="Petrault">Maud Petrault</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Laloux, Charlotte" sort="Laloux, Charlotte" uniqKey="Laloux C" first="Charlotte" last="Laloux">Charlotte Laloux</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Jonneaux, Aurelie" sort="Jonneaux, Aurelie" uniqKey="Jonneaux A" first="Aurélie" last="Jonneaux">Aurélie Jonneaux</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Ryckewaert, Gilles" sort="Ryckewaert, Gilles" uniqKey="Ryckewaert G" first="Gilles" last="Ryckewaert">Gilles Ryckewaert</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Garcon, Guillaume" sort="Garcon, Guillaume" uniqKey="Garcon G" first="Guillaume" last="Garçon">Guillaume Garçon</name><affiliation><nlm:aff id="aff6"></nlm:aff></affiliation></author><author><name sortKey="Rouaix, Nathalie" sort="Rouaix, Nathalie" uniqKey="Rouaix N" first="Nathalie" last="Rouaix">Nathalie Rouaix</name><affiliation><nlm:aff id="aff7"></nlm:aff></affiliation></author><author><name sortKey="Duhamel, Alain" sort="Duhamel, Alain" uniqKey="Duhamel A" first="Alain" last="Duhamel">Alain Duhamel</name><affiliation><nlm:aff id="aff8"></nlm:aff></affiliation></author><author><name sortKey="Jissendi, Patrice" sort="Jissendi, Patrice" uniqKey="Jissendi P" first="Patrice" last="Jissendi">Patrice Jissendi</name><affiliation><nlm:aff id="aff9"></nlm:aff></affiliation></author><author><name sortKey="Dujardin, Kathy" sort="Dujardin, Kathy" uniqKey="Dujardin K" first="Kathy" last="Dujardin">Kathy Dujardin</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Auger, Florent" sort="Auger, Florent" uniqKey="Auger F" first="Florent" last="Auger">Florent Auger</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation><affiliation><nlm:aff id="aff10"></nlm:aff></affiliation></author><author><name sortKey="Ravasi, Laura" sort="Ravasi, Laura" uniqKey="Ravasi L" first="Laura" last="Ravasi">Laura Ravasi</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation><affiliation><nlm:aff id="aff11"></nlm:aff></affiliation></author><author><name sortKey="Hopes, Lucie" sort="Hopes, Lucie" uniqKey="Hopes L" first="Lucie" last="Hopes">Lucie Hopes</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Grolez, Guillaume" sort="Grolez, Guillaume" uniqKey="Grolez G" first="Guillaume" last="Grolez">Guillaume Grolez</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Firdaus, Wance" sort="Firdaus, Wance" uniqKey="Firdaus W" first="Wance" last="Firdaus">Wance Firdaus</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Sablonniere, Bernard" sort="Sablonniere, Bernard" uniqKey="Sablonniere B" first="Bernard" last="Sablonnière">Bernard Sablonnière</name><affiliation><nlm:aff id="aff7"></nlm:aff></affiliation></author><author><name sortKey="Strubi Vuillaume, Isabelle" sort="Strubi Vuillaume, Isabelle" uniqKey="Strubi Vuillaume I" first="Isabelle" last="Strubi-Vuillaume">Isabelle Strubi-Vuillaume</name><affiliation><nlm:aff id="aff7"></nlm:aff></affiliation></author><author><name sortKey="Zahr, Noel" sort="Zahr, Noel" uniqKey="Zahr N" first="Noel" last="Zahr">Noel Zahr</name><affiliation><nlm:aff id="aff12"></nlm:aff></affiliation></author><author><name sortKey="Destee, Alain" sort="Destee, Alain" uniqKey="Destee A" first="Alain" last="Destée">Alain Destée</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff13"></nlm:aff></affiliation></author><author><name sortKey="Corvol, Jean Christophe" sort="Corvol, Jean Christophe" uniqKey="Corvol J" first="Jean-Christophe" last="Corvol">Jean-Christophe Corvol</name><affiliation><nlm:aff id="aff14"></nlm:aff></affiliation></author><author><name sortKey="Poltl, Dominik" sort="Poltl, Dominik" uniqKey="Poltl D" first="Dominik" last="Pöltl">Dominik Pöltl</name><affiliation><nlm:aff id="aff15"></nlm:aff></affiliation><affiliation><nlm:aff id="aff16"></nlm:aff></affiliation></author><author><name sortKey="Leist, Marcel" sort="Leist, Marcel" uniqKey="Leist M" first="Marcel" last="Leist">Marcel Leist</name><affiliation><nlm:aff id="aff15"></nlm:aff></affiliation><affiliation><nlm:aff id="aff16"></nlm:aff></affiliation></author><author><name sortKey="Rose, Christian" sort="Rose, Christian" uniqKey="Rose C" first="Christian" last="Rose">Christian Rose</name><affiliation><nlm:aff id="aff17"></nlm:aff></affiliation></author><author><name sortKey="Defebvre, Luc" sort="Defebvre, Luc" uniqKey="Defebvre L" first="Luc" last="Defebvre">Luc Defebvre</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Marchetti, Philippe" sort="Marchetti, Philippe" uniqKey="Marchetti P" first="Philippe" last="Marchetti">Philippe Marchetti</name><affiliation><nlm:aff id="aff5"></nlm:aff></affiliation></author><author><name sortKey="Cabantchik, Z Ioav" sort="Cabantchik, Z Ioav" uniqKey="Cabantchik Z" first="Z. Ioav" last="Cabantchik">Z. Ioav Cabantchik</name><affiliation><nlm:aff id="aff18"></nlm:aff></affiliation></author><author><name sortKey="Bordet, Regis" sort="Bordet, Regis" uniqKey="Bordet R" first="Régis" last="Bordet">Régis Bordet</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author></analytic><series><title level="j">Antioxidants & Redox Signaling</title><idno type="ISSN">1523-0864</idno><idno type="eISSN">1557-7716</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Abstract</title><p><bold><italic>Aims:</italic></bold> The pathophysiological role of iron in Parkinson's disease (PD) was assessed by a chelation strategy aimed at reducing oxidative damage associated with regional iron deposition without affecting circulating metals. Translational cell and animal models provided concept proofs and a delayed-start (DS) treatment paradigm, the basis for preliminary clinical assessments. <bold><italic>Results:</italic></bold> For translational studies, we assessed the effect of oxidative insults in mice systemically prechelated with deferiprone (DFP) by following motor functions, striatal dopamine (HPLC and MRI-PET), and brain iron deposition (relaxation-R2*-MRI) aided by spectroscopic measurements of neuronal labile iron (with fluorescence-sensitive iron sensors) and oxidative damage by markers of protein, lipid, and DNA modification. DFP significantly reduced labile iron and biological damage in oxidation-stressed cells and animals, improving motor functions while raising striatal dopamine. For a pilot, double-blind, placebo-controlled randomized clinical trial, early-stage Parkinson's patients on stabilized dopamine regimens enrolled in a 12-month single-center study with DFP (30 mg/kg/day). Based on a 6-month DS paradigm, early-start patients (<italic>n</italic>=19) compared to DS patients (<italic>n</italic>=18) (37/40 completed) responded significantly earlier and sustainably to treatment in both substantia nigra iron deposits (R2* MRI) and Unified Parkinson's Disease Rating Scale motor indicators of disease progression (<italic>p</italic><0.03 and <italic>p</italic><0.04, respectively). Apart from three rapidly resolved neutropenia cases, safety was maintained throughout the trial. <bold><italic>Innovation:</italic></bold> A moderate iron chelation regimen that avoids changes in systemic iron levels may constitute a novel therapeutic modality for PD. <bold><italic>Conclusions:</italic></bold> The therapeutic features of a chelation modality established in translational models and in pilot clinical trials warrant comprehensive evaluation of symptomatic and/or disease-modifying potential of chelation in PD. <italic>Antioxid. Redox Signal</italic>. 21, 195–210.</p></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>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Antioxid Redox Signal</journal-id><journal-id journal-id-type="iso-abbrev">Antioxid. Redox Signal</journal-id><journal-id journal-id-type="publisher-id">ars</journal-id><journal-title-group><journal-title>Antioxidants & Redox Signaling</journal-title></journal-title-group><issn pub-type="ppub">1523-0864</issn><issn pub-type="epub">1557-7716</issn><publisher><publisher-name>Mary Ann Liebert, Inc.</publisher-name><publisher-loc>140 Huguenot Street, 3rd FloorNew Rochelle, NY 10801USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24251381</article-id><article-id pub-id-type="pmc">4060813</article-id><article-id pub-id-type="publisher-id">10.1089/ars.2013.5593</article-id><article-id pub-id-type="doi">10.1089/ars.2013.5593</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Research Communication</subject></subj-group></article-categories><title-group><article-title>Targeting Chelatable Iron as a Therapeutic Modality in Parkinson's Disease</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Devos</surname><given-names>David</given-names></name><xref ref-type="aff" rid="aff1"><sup>1,</sup></xref><xref ref-type="aff" rid="aff2"><sup>2,</sup></xref><xref ref-type="aff" rid="aff3"><sup>3,</sup></xref><role><sup>*</sup></role><fn id="fn1" fn-type="equal"><label><sup>*</sup></label><p>These authors contributed equally to this work.</p></fn></contrib><contrib contrib-type="author"><name><surname>Moreau</surname><given-names>Caroline</given-names></name><xref ref-type="aff" rid="aff2"><sup>2,</sup></xref><xref ref-type="aff" rid="aff3"><sup>3,</sup></xref><xref ref-type="fn" rid="fn1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Devedjian</surname><given-names>Jean Christophe</given-names></name><xref ref-type="aff" rid="aff3"><sup>3,</sup></xref><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kluza</surname><given-names>Jérome</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Petrault</surname><given-names>Maud</given-names></name><xref ref-type="aff" rid="aff1"><sup>1,</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Laloux</surname><given-names>Charlotte</given-names></name><xref ref-type="aff" rid="aff1"><sup>1,</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jonneaux</surname><given-names>Aurélie</given-names></name><xref ref-type="aff" rid="aff1"><sup>1,</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ryckewaert</surname><given-names>Gilles</given-names></name><xref ref-type="aff" rid="aff2"><sup>2,</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Garçon</surname><given-names>Guillaume</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rouaix</surname><given-names>Nathalie</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Duhamel</surname><given-names>Alain</given-names></name><xref ref-type="aff" rid="aff8"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jissendi</surname><given-names>Patrice</given-names></name><xref ref-type="aff" rid="aff9"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dujardin</surname><given-names>Kathy</given-names></name><xref ref-type="aff" rid="aff2"><sup>2,</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Auger</surname><given-names>Florent</given-names></name><xref ref-type="aff" rid="aff3"><sup>3,</sup></xref><xref ref-type="aff" rid="aff10"><sup>10</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ravasi</surname><given-names>Laura</given-names></name><xref ref-type="aff" rid="aff3"><sup>3,</sup></xref><xref ref-type="aff" rid="aff11"><sup>11</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hopes</surname><given-names>Lucie</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Grolez</surname><given-names>Guillaume</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Firdaus</surname><given-names>Wance</given-names></name><xref ref-type="aff" rid="aff1"><sup>1,</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sablonnière</surname><given-names>Bernard</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Strubi-Vuillaume</surname><given-names>Isabelle</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zahr</surname><given-names>Noel</given-names></name><xref ref-type="aff" rid="aff12"><sup>12</sup></xref></contrib><contrib contrib-type="author"><name><surname>Destée</surname><given-names>Alain</given-names></name><xref ref-type="aff" rid="aff2"><sup>2,</sup></xref><xref ref-type="aff" rid="aff13"><sup>13</sup></xref></contrib><contrib contrib-type="author"><name><surname>Corvol</surname><given-names>Jean-Christophe</given-names></name><xref ref-type="aff" rid="aff14"><sup>14</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pöltl</surname><given-names>Dominik</given-names></name><xref ref-type="aff" rid="aff15"><sup>15,</sup></xref><xref ref-type="aff" rid="aff16"><sup>16</sup></xref></contrib><contrib contrib-type="author"><name><surname>Leist</surname><given-names>Marcel</given-names></name><xref ref-type="aff" rid="aff15"><sup>15,</sup></xref><xref ref-type="aff" rid="aff16"><sup>16</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rose</surname><given-names>Christian</given-names></name><xref ref-type="aff" rid="aff17"><sup>17</sup></xref></contrib><contrib contrib-type="author"><name><surname>Defebvre</surname><given-names>Luc</given-names></name><xref ref-type="aff" rid="aff2"><sup>2,</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Marchetti</surname><given-names>Philippe</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cabantchik</surname><given-names>Z. Ioav</given-names></name><xref ref-type="aff" rid="aff18"><sup>18,</sup></xref><xref ref-type="fn" rid="fn1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bordet</surname><given-names>Régis</given-names></name><xref ref-type="aff" rid="aff1"><sup>1,</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><aff id="aff1"><label><sup>1</sup></label>Department of Medical Pharmacology, Faculté de Médecine Lille2,<institution>Lille Nord de France University</institution>, CHU Lille, Lille,<country>France</country>.</aff><aff id="aff2"><label><sup>2</sup></label>Department of Movement Disorders and Neurology,<institution>Lille Nord de France University</institution>, CHU Lille, Lille,<country>France</country>.</aff><aff id="aff3"><label><sup>3</sup></label>EA 1046,<institution>Lille Nord de France University</institution>, Lille,<country>France</country>.</aff><aff id="aff4"><label><sup>4</sup></label>University of the Littoral,<institution>Lille Nord de France University</institution>, Lille,<country>France</country>.</aff><aff id="aff5"><label><sup>5</sup></label>Unit 837 Equipe 4 Inserm and Faculté de Médecine,<institution>Lille Nord de France University</institution>, Lille,<country>France</country>.</aff><aff id="aff6"><label><sup>6</sup></label>Department of Toxicology,<institution>Public Health and Environment</institution>, EA4483, Faculté des Sciences Pharmaceutiques et Biologiques de Lille, Lille,<country>France</country>.</aff><aff id="aff7"><label><sup>7</sup></label>Department of Molecular Biology,<institution>Lille Nord de France University</institution>, CHU Lille, Lille,<country>France</country>.</aff><aff id="aff8"><label><sup>8</sup></label>Department of Biostatistics,<institution>Lille Nord de France University</institution>, CHU Lille, Lille,<country>France</country>.</aff><aff id="aff9"><label><sup>9</sup></label>Department Neuroradiology,<institution>Lille Nord de France University</institution>, CHU Lille, Lille,<country>France</country>.</aff><aff id="aff10"><label><sup>10</sup></label>Department of Animal Neuroradiology,<institution>Lille Nord de France University</institution>, Lille,<country>France</country>.</aff><aff id="aff11"><label><sup>11</sup></label>Department of Animal Nuclear Medicine,<institution>Lille Nord de France University</institution>, Lille,<country>France</country>.</aff><aff id="aff12"><label><sup>12</sup></label>Department of Pharmacology, APHP,<institution>Pitié-Salpêtrière Hospital</institution>, Paris,<country>France</country>.</aff><aff id="aff13"><label><sup>13</sup></label><institution>INSERM U837/6 JPARC Université Lille Nord de France</institution>, Lille,<country>France</country>.</aff><aff id="aff14"><label><sup>14</sup></label>INSERM, CR-ICM, UMRS975, CNRS UMR7225, UPMC, INSERM, CIC-9503, Department of Neurology,<institution>Pitié-Salpêtrière Hospital</institution>, Paris,<country>France</country>.</aff><aff id="aff15"><label><sup>15</sup></label>Doerenkamp-Zbinden Chair for In Vitro Toxicology and Biomedicine,<institution>University of Konstanz</institution>, Konstanz,<country>Germany</country>.</aff><aff id="aff16"><label><sup>16</sup></label>Konstanz Research School Chemical Biology,<institution>University of Konstanz</institution>, Konstanz,<country>Germany</country>.</aff><aff id="aff17"><label><sup>17</sup></label>Department of Hematology, Hôpital Saint Vincent de Paul,<institution>Lille Nord de France University</institution>, Lille,<country>France</country>.</aff><aff id="aff18"><label><sup>18</sup></label>Della Pergola Chair,<institution>Alexander Silberman Institute of Life Sciences</institution>, Hebrew University, Jerusalem,<country>Israel</country>.</aff></contrib-group><author-notes><corresp><addr-line>Address correspondence to:</addr-line><addr-line><italic>Dr. David Devos</italic></addr-line><addr-line><italic>Département de Pharmacologie Médicale</italic></addr-line><addr-line><italic>Faculté de Médecine Lille2</italic></addr-line><institution><italic>Université Lille Nord de France</italic></institution><addr-line><italic>CHRU de Lille</italic></addr-line><addr-line><italic>Lille F-59037</italic></addr-line><country>France</country><break></break><italic>E-mail:</italic><email xlink:href="mailto:david.devos@chru-lille.fr">david.devos@chru-lille.fr</email></corresp></author-notes><pub-date pub-type="ppub"><day>10</day><month>7</month><year>2014</year><pmc-comment>string-date: July 10, 2014</pmc-comment>
</pub-date><pub-date pub-type="pmc-release"><day>10</day><month>7</month><year>2014</year><pmc-comment>string-date: July 10, 2014</pmc-comment>
</pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>21</volume><issue>2</issue><fpage>195</fpage><lpage>210</lpage><history><date date-type="received"><day>16</day><month>8</month><year>2013</year><pmc-comment>string-date: Date of first submission to ARS Central, August 16, 2013</pmc-comment>
</date><date date-type="rev-recd"><day>04</day><month>11</month><year>2013</year><pmc-comment>string-date: date of final revised submission, November 4, 2013</pmc-comment>
</date><date date-type="accepted"><day>18</day><month>11</month><year>2013</year><pmc-comment>string-date: date of acceptance, November 18, 2013</pmc-comment>
</date></history><permissions><copyright-statement>Copyright 2014, Mary Ann Liebert, Inc.</copyright-statement><copyright-year>2014</copyright-year></permissions><self-uri content-type="pdf" xlink:type="simple" xlink:href="ars.2013.5593.pdf"></self-uri><abstract><title>Abstract</title><p><bold><italic>Aims:</italic></bold> The pathophysiological role of iron in Parkinson's disease (PD) was assessed by a chelation strategy aimed at reducing oxidative damage associated with regional iron deposition without affecting circulating metals. Translational cell and animal models provided concept proofs and a delayed-start (DS) treatment paradigm, the basis for preliminary clinical assessments. <bold><italic>Results:</italic></bold> For translational studies, we assessed the effect of oxidative insults in mice systemically prechelated with deferiprone (DFP) by following motor functions, striatal dopamine (HPLC and MRI-PET), and brain iron deposition (relaxation-R2*-MRI) aided by spectroscopic measurements of neuronal labile iron (with fluorescence-sensitive iron sensors) and oxidative damage by markers of protein, lipid, and DNA modification. DFP significantly reduced labile iron and biological damage in oxidation-stressed cells and animals, improving motor functions while raising striatal dopamine. For a pilot, double-blind, placebo-controlled randomized clinical trial, early-stage Parkinson's patients on stabilized dopamine regimens enrolled in a 12-month single-center study with DFP (30 mg/kg/day). Based on a 6-month DS paradigm, early-start patients (<italic>n</italic>=19) compared to DS patients (<italic>n</italic>=18) (37/40 completed) responded significantly earlier and sustainably to treatment in both substantia nigra iron deposits (R2* MRI) and Unified Parkinson's Disease Rating Scale motor indicators of disease progression (<italic>p</italic><0.03 and <italic>p</italic><0.04, respectively). Apart from three rapidly resolved neutropenia cases, safety was maintained throughout the trial. <bold><italic>Innovation:</italic></bold> A moderate iron chelation regimen that avoids changes in systemic iron levels may constitute a novel therapeutic modality for PD. <bold><italic>Conclusions:</italic></bold> The therapeutic features of a chelation modality established in translational models and in pilot clinical trials warrant comprehensive evaluation of symptomatic and/or disease-modifying potential of chelation in PD. <italic>Antioxid. Redox Signal</italic>. 21, 195–210.</p></abstract><counts><fig-count count="7"></fig-count><table-count count="1"></table-count><ref-count count="75"></ref-count><page-count count="16"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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