Human Fetal Cell Therapy in Huntington's Disease: A Randomized, Multicenter, Phase II Trial
Background Huntington's disease is a rare, severe, inherited neurodegenerative disease in which we assessed the safety and efficacy of grafting human fetal ganglionic eminence intrastriatally. Methods Patients at the early stage of the disease were enrolled in the Multicentric Intracerebral Gra...
Gespeichert in:
| Veröffentlicht in: | Movement disorders 2020-08, Vol.35 (8), p.1323-1335 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1335 |
|---|---|
| container_issue | 8 |
| container_start_page | 1323 |
| container_title | Movement disorders |
| container_volume | 35 |
| creator | Bachoud‐Lévi, Anne‐Catherine Schramm, Catherine Remy, Philippe Aubin, Ghislaine Blond, Serge Bocket, Laurence Brugières, Pierre Calvas, Fabienne Calvier, Elisabeth Cassim, François Challine, Dominique Gagou, Clarisse Scherer Langavant, Laurent Cleret Collier, Francis Cottencin, Olivier David, Philippe Damier, Philippe Delliaux, Marie Delmaire, Christine Delval, Arnaud Démonet, Jean‐François Descamps, Philippe Gaura, Véronique Gohier, Bénédicte Goldman, Serge Haddad, Bassam Izopet, Jacques Jeny, Roland Kerr‐Conte, Julie Krystowiak, Pierre Lalanne, Christophe Lavisse, Sonia Lefaucheur, Jean‐Pascal Lemoine, Laurie Levivier, Marc Lotterie, Jean‐Albert Lunel‐Fabiani, Françoise Maison, Patrick Massager, Nicolas Massart, Renaud Menei, Philippe Montero‐Menei, Claudia Neveu, Isabelle Parant, Olivier Pautot, Vivien Payoux, Pierre Pereon, Yann Rialland, Amandine Rosser, Anne Rouard, Hélène Schmitz, David Simonetta‐Moreau, Marion Simonin, Clémence Slama, Hichem Sol, Jean‐Christophe Supiot, Frédéric Tanguy, Jean‐Yves Tenenbaum, Liliane Verny, Christophe Youssov, Katia Peschanski, Marc Audureau, Etienne Palfi, Stéphane Hantraye, Philippe |
| description | Background
Huntington's disease is a rare, severe, inherited neurodegenerative disease in which we assessed the safety and efficacy of grafting human fetal ganglionic eminence intrastriatally.
Methods
Patients at the early stage of the disease were enrolled in the Multicentric Intracerebral Grafting in Huntington's Disease trial, a delayed‐start phase II randomized study. After a run‐in period of 12 months, patients were randomized at month 12 to either the treatment group (transplanted at month 13–month 14) or the control group and secondarily treated 20 months later (month 33–month 34). The primary outcome was total motor score compared between both groups 20 months postrandomization (month 32). Secondary outcomes included clinical, imaging, and electrophysiological findings and a comparison of pregraft and postgraft total motor score slopes during the entire study period (month 0–month 52) regardless of the time of transplant.
Results
Of 54 randomized patients, 45 were transplanted; 26 immediately (treatment) and 19 delayed (control). Mean total motor score at month 32 did not differ between groups (treated controls difference in means adjusted for M12: +2.9 [95% confidence interval, −2.8 to 8.6]; P = 0.31). Its rate of decline after transplantation was similar to that before transplantation. A total of 27 severe adverse events were recorded in the randomized patients, 10 of which were related to the transplant procedure. Improvement of procedures during the trial significantly decreased the frequency of surgical events.We found antihuman leucocytes antigen antibodies in 40% of the patients.
Conclusion
No clinical benefit was found in this trial. This may have been related to graft rejection. Ectopia and high track number negatively influence the graft outcome. Procedural adjustments substantially improved surgical safety. (ClinicalTrials.gov NCT00190450.) © 2020 International Parkinson and Movement Disorder Society |
| doi_str_mv | 10.1002/mds.28201 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_inserm_03549919v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2432444477</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3401-e042e0b8afeedfcaa8630642f7b599ff3a3f88940db626848bda2a1bb791a7cf3</originalsourceid><addsrcrecordid>eNp10U1v1DAQBmALUdGlcOAPIEscAGnT-iMfDrfVlnZX2goEy4mDNUnGrKvE2doJaPn1uE3bQyV88eXROzN6CXnD2SlnTJx1TTgVSjD-jMx4JnmiRFY8JzOmVJZIrrJj8jKEa8Y4z3j-ghxLked5VpYz8nM1duDoBQ7Q0iW2Ld3u0MP-QK2jq9EN1v0aevc-0HMbEAJ-ogv6DVzTd_YvNnN6NbaDrdEN6Of06y4Kul7TrbfQviJHBtqAr-__E_Lj4vN2uUo2Xy7Xy8UmqWXKeIIsFcgqBQaxMTWAyiXLU2GKKq5ojARplCpT1lS5yFWqqgYE8KoqSg5FbeQJmU-5O2j13tsO_EH3YPVqsdHWBfSdZjJLy5KXv3nkHya-9_3NiGHQnQ11PB0c9mPQIhUpK4s4MNJ3T-h1P3oXj4lKijS-oojq46Rq34fg0TwuwZm-LUjHgvRdQdG-vU8cqw6bR_nQSARnE_hjWzz8P0lfnX-fIv8Bo6KXqg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2432444477</pqid></control><display><type>article</type><title>Human Fetal Cell Therapy in Huntington's Disease: A Randomized, Multicenter, Phase II Trial</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Bachoud‐Lévi, Anne‐Catherine ; Schramm, Catherine ; Remy, Philippe ; Aubin, Ghislaine ; Blond, Serge ; Bocket, Laurence ; Brugières, Pierre ; Calvas, Fabienne ; Calvier, Elisabeth ; Cassim, François ; Challine, Dominique ; Gagou, Clarisse Scherer ; Langavant, Laurent Cleret ; Collier, Francis ; Cottencin, Olivier ; David, Philippe ; Damier, Philippe ; Delliaux, Marie ; Delmaire, Christine ; Delval, Arnaud ; Démonet, Jean‐François ; Descamps, Philippe ; Gaura, Véronique ; Gohier, Bénédicte ; Goldman, Serge ; Haddad, Bassam ; Izopet, Jacques ; Jeny, Roland ; Kerr‐Conte, Julie ; Krystowiak, Pierre ; Lalanne, Christophe ; Lavisse, Sonia ; Lefaucheur, Jean‐Pascal ; Lemoine, Laurie ; Levivier, Marc ; Lotterie, Jean‐Albert ; Lunel‐Fabiani, Françoise ; Maison, Patrick ; Massager, Nicolas ; Massart, Renaud ; Menei, Philippe ; Montero‐Menei, Claudia ; Neveu, Isabelle ; Parant, Olivier ; Pautot, Vivien ; Payoux, Pierre ; Pereon, Yann ; Rialland, Amandine ; Rosser, Anne ; Rouard, Hélène ; Schmitz, David ; Simonetta‐Moreau, Marion ; Simonin, Clémence ; Slama, Hichem ; Sol, Jean‐Christophe ; Supiot, Frédéric ; Tanguy, Jean‐Yves ; Tenenbaum, Liliane ; Verny, Christophe ; Youssov, Katia ; Peschanski, Marc ; Audureau, Etienne ; Palfi, Stéphane ; Hantraye, Philippe</creator><creatorcontrib>Bachoud‐Lévi, Anne‐Catherine ; Schramm, Catherine ; Remy, Philippe ; Aubin, Ghislaine ; Blond, Serge ; Bocket, Laurence ; Brugières, Pierre ; Calvas, Fabienne ; Calvier, Elisabeth ; Cassim, François ; Challine, Dominique ; Gagou, Clarisse Scherer ; Langavant, Laurent Cleret ; Collier, Francis ; Cottencin, Olivier ; David, Philippe ; Damier, Philippe ; Delliaux, Marie ; Delmaire, Christine ; Delval, Arnaud ; Démonet, Jean‐François ; Descamps, Philippe ; Gaura, Véronique ; Gohier, Bénédicte ; Goldman, Serge ; Haddad, Bassam ; Izopet, Jacques ; Jeny, Roland ; Kerr‐Conte, Julie ; Krystowiak, Pierre ; Lalanne, Christophe ; Lavisse, Sonia ; Lefaucheur, Jean‐Pascal ; Lemoine, Laurie ; Levivier, Marc ; Lotterie, Jean‐Albert ; Lunel‐Fabiani, Françoise ; Maison, Patrick ; Massager, Nicolas ; Massart, Renaud ; Menei, Philippe ; Montero‐Menei, Claudia ; Neveu, Isabelle ; Parant, Olivier ; Pautot, Vivien ; Payoux, Pierre ; Pereon, Yann ; Rialland, Amandine ; Rosser, Anne ; Rouard, Hélène ; Schmitz, David ; Simonetta‐Moreau, Marion ; Simonin, Clémence ; Slama, Hichem ; Sol, Jean‐Christophe ; Supiot, Frédéric ; Tanguy, Jean‐Yves ; Tenenbaum, Liliane ; Verny, Christophe ; Youssov, Katia ; Peschanski, Marc ; Audureau, Etienne ; Palfi, Stéphane ; Hantraye, Philippe ; on behalf the Multicentric Intracerebral Grafting in Huntington's Disease Group</creatorcontrib><description>Background
Huntington's disease is a rare, severe, inherited neurodegenerative disease in which we assessed the safety and efficacy of grafting human fetal ganglionic eminence intrastriatally.
Methods
Patients at the early stage of the disease were enrolled in the Multicentric Intracerebral Grafting in Huntington's Disease trial, a delayed‐start phase II randomized study. After a run‐in period of 12 months, patients were randomized at month 12 to either the treatment group (transplanted at month 13–month 14) or the control group and secondarily treated 20 months later (month 33–month 34). The primary outcome was total motor score compared between both groups 20 months postrandomization (month 32). Secondary outcomes included clinical, imaging, and electrophysiological findings and a comparison of pregraft and postgraft total motor score slopes during the entire study period (month 0–month 52) regardless of the time of transplant.
Results
Of 54 randomized patients, 45 were transplanted; 26 immediately (treatment) and 19 delayed (control). Mean total motor score at month 32 did not differ between groups (treated controls difference in means adjusted for M12: +2.9 [95% confidence interval, −2.8 to 8.6]; P = 0.31). Its rate of decline after transplantation was similar to that before transplantation. A total of 27 severe adverse events were recorded in the randomized patients, 10 of which were related to the transplant procedure. Improvement of procedures during the trial significantly decreased the frequency of surgical events.We found antihuman leucocytes antigen antibodies in 40% of the patients.
Conclusion
No clinical benefit was found in this trial. This may have been related to graft rejection. Ectopia and high track number negatively influence the graft outcome. Procedural adjustments substantially improved surgical safety. (ClinicalTrials.gov NCT00190450.) © 2020 International Parkinson and Movement Disorder Society</description><identifier>ISSN: 0885-3185</identifier><identifier>EISSN: 1531-8257</identifier><identifier>DOI: 10.1002/mds.28201</identifier><identifier>PMID: 32666599</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Cell therapy ; Cell- and Tissue-Based Therapy ; Cellular Biology ; Fetuses ; Graft rejection ; Humans ; Huntington Disease - therapy ; Huntington's disease ; Huntingtons disease ; Leukocytes ; Life Sciences ; MIG‐HD ; Motor task performance ; Movement disorders ; Neurodegenerative Diseases ; Patients ; phase 2 trial ; Transplantation ; Transplants & implants</subject><ispartof>Movement disorders, 2020-08, Vol.35 (8), p.1323-1335</ispartof><rights>2020 International Parkinson and Movement Disorder Society</rights><rights>2020 International Parkinson and Movement Disorder Society.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3401-e042e0b8afeedfcaa8630642f7b599ff3a3f88940db626848bda2a1bb791a7cf3</citedby><cites>FETCH-LOGICAL-c3401-e042e0b8afeedfcaa8630642f7b599ff3a3f88940db626848bda2a1bb791a7cf3</cites><orcidid>0000-0003-3000-2210</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmds.28201$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmds.28201$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32666599$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-03549919$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Bachoud‐Lévi, Anne‐Catherine</creatorcontrib><creatorcontrib>Schramm, Catherine</creatorcontrib><creatorcontrib>Remy, Philippe</creatorcontrib><creatorcontrib>Aubin, Ghislaine</creatorcontrib><creatorcontrib>Blond, Serge</creatorcontrib><creatorcontrib>Bocket, Laurence</creatorcontrib><creatorcontrib>Brugières, Pierre</creatorcontrib><creatorcontrib>Calvas, Fabienne</creatorcontrib><creatorcontrib>Calvier, Elisabeth</creatorcontrib><creatorcontrib>Cassim, François</creatorcontrib><creatorcontrib>Challine, Dominique</creatorcontrib><creatorcontrib>Gagou, Clarisse Scherer</creatorcontrib><creatorcontrib>Langavant, Laurent Cleret</creatorcontrib><creatorcontrib>Collier, Francis</creatorcontrib><creatorcontrib>Cottencin, Olivier</creatorcontrib><creatorcontrib>David, Philippe</creatorcontrib><creatorcontrib>Damier, Philippe</creatorcontrib><creatorcontrib>Delliaux, Marie</creatorcontrib><creatorcontrib>Delmaire, Christine</creatorcontrib><creatorcontrib>Delval, Arnaud</creatorcontrib><creatorcontrib>Démonet, Jean‐François</creatorcontrib><creatorcontrib>Descamps, Philippe</creatorcontrib><creatorcontrib>Gaura, Véronique</creatorcontrib><creatorcontrib>Gohier, Bénédicte</creatorcontrib><creatorcontrib>Goldman, Serge</creatorcontrib><creatorcontrib>Haddad, Bassam</creatorcontrib><creatorcontrib>Izopet, Jacques</creatorcontrib><creatorcontrib>Jeny, Roland</creatorcontrib><creatorcontrib>Kerr‐Conte, Julie</creatorcontrib><creatorcontrib>Krystowiak, Pierre</creatorcontrib><creatorcontrib>Lalanne, Christophe</creatorcontrib><creatorcontrib>Lavisse, Sonia</creatorcontrib><creatorcontrib>Lefaucheur, Jean‐Pascal</creatorcontrib><creatorcontrib>Lemoine, Laurie</creatorcontrib><creatorcontrib>Levivier, Marc</creatorcontrib><creatorcontrib>Lotterie, Jean‐Albert</creatorcontrib><creatorcontrib>Lunel‐Fabiani, Françoise</creatorcontrib><creatorcontrib>Maison, Patrick</creatorcontrib><creatorcontrib>Massager, Nicolas</creatorcontrib><creatorcontrib>Massart, Renaud</creatorcontrib><creatorcontrib>Menei, Philippe</creatorcontrib><creatorcontrib>Montero‐Menei, Claudia</creatorcontrib><creatorcontrib>Neveu, Isabelle</creatorcontrib><creatorcontrib>Parant, Olivier</creatorcontrib><creatorcontrib>Pautot, Vivien</creatorcontrib><creatorcontrib>Payoux, Pierre</creatorcontrib><creatorcontrib>Pereon, Yann</creatorcontrib><creatorcontrib>Rialland, Amandine</creatorcontrib><creatorcontrib>Rosser, Anne</creatorcontrib><creatorcontrib>Rouard, Hélène</creatorcontrib><creatorcontrib>Schmitz, David</creatorcontrib><creatorcontrib>Simonetta‐Moreau, Marion</creatorcontrib><creatorcontrib>Simonin, Clémence</creatorcontrib><creatorcontrib>Slama, Hichem</creatorcontrib><creatorcontrib>Sol, Jean‐Christophe</creatorcontrib><creatorcontrib>Supiot, Frédéric</creatorcontrib><creatorcontrib>Tanguy, Jean‐Yves</creatorcontrib><creatorcontrib>Tenenbaum, Liliane</creatorcontrib><creatorcontrib>Verny, Christophe</creatorcontrib><creatorcontrib>Youssov, Katia</creatorcontrib><creatorcontrib>Peschanski, Marc</creatorcontrib><creatorcontrib>Audureau, Etienne</creatorcontrib><creatorcontrib>Palfi, Stéphane</creatorcontrib><creatorcontrib>Hantraye, Philippe</creatorcontrib><creatorcontrib>on behalf the Multicentric Intracerebral Grafting in Huntington's Disease Group</creatorcontrib><title>Human Fetal Cell Therapy in Huntington's Disease: A Randomized, Multicenter, Phase II Trial</title><title>Movement disorders</title><addtitle>Mov Disord</addtitle><description>Background
Huntington's disease is a rare, severe, inherited neurodegenerative disease in which we assessed the safety and efficacy of grafting human fetal ganglionic eminence intrastriatally.
Methods
Patients at the early stage of the disease were enrolled in the Multicentric Intracerebral Grafting in Huntington's Disease trial, a delayed‐start phase II randomized study. After a run‐in period of 12 months, patients were randomized at month 12 to either the treatment group (transplanted at month 13–month 14) or the control group and secondarily treated 20 months later (month 33–month 34). The primary outcome was total motor score compared between both groups 20 months postrandomization (month 32). Secondary outcomes included clinical, imaging, and electrophysiological findings and a comparison of pregraft and postgraft total motor score slopes during the entire study period (month 0–month 52) regardless of the time of transplant.
Results
Of 54 randomized patients, 45 were transplanted; 26 immediately (treatment) and 19 delayed (control). Mean total motor score at month 32 did not differ between groups (treated controls difference in means adjusted for M12: +2.9 [95% confidence interval, −2.8 to 8.6]; P = 0.31). Its rate of decline after transplantation was similar to that before transplantation. A total of 27 severe adverse events were recorded in the randomized patients, 10 of which were related to the transplant procedure. Improvement of procedures during the trial significantly decreased the frequency of surgical events.We found antihuman leucocytes antigen antibodies in 40% of the patients.
Conclusion
No clinical benefit was found in this trial. This may have been related to graft rejection. Ectopia and high track number negatively influence the graft outcome. Procedural adjustments substantially improved surgical safety. (ClinicalTrials.gov NCT00190450.) © 2020 International Parkinson and Movement Disorder Society</description><subject>Cell therapy</subject><subject>Cell- and Tissue-Based Therapy</subject><subject>Cellular Biology</subject><subject>Fetuses</subject><subject>Graft rejection</subject><subject>Humans</subject><subject>Huntington Disease - therapy</subject><subject>Huntington's disease</subject><subject>Huntingtons disease</subject><subject>Leukocytes</subject><subject>Life Sciences</subject><subject>MIG‐HD</subject><subject>Motor task performance</subject><subject>Movement disorders</subject><subject>Neurodegenerative Diseases</subject><subject>Patients</subject><subject>phase 2 trial</subject><subject>Transplantation</subject><subject>Transplants & implants</subject><issn>0885-3185</issn><issn>1531-8257</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10U1v1DAQBmALUdGlcOAPIEscAGnT-iMfDrfVlnZX2goEy4mDNUnGrKvE2doJaPn1uE3bQyV88eXROzN6CXnD2SlnTJx1TTgVSjD-jMx4JnmiRFY8JzOmVJZIrrJj8jKEa8Y4z3j-ghxLked5VpYz8nM1duDoBQ7Q0iW2Ld3u0MP-QK2jq9EN1v0aevc-0HMbEAJ-ogv6DVzTd_YvNnN6NbaDrdEN6Of06y4Kul7TrbfQviJHBtqAr-__E_Lj4vN2uUo2Xy7Xy8UmqWXKeIIsFcgqBQaxMTWAyiXLU2GKKq5ojARplCpT1lS5yFWqqgYE8KoqSg5FbeQJmU-5O2j13tsO_EH3YPVqsdHWBfSdZjJLy5KXv3nkHya-9_3NiGHQnQ11PB0c9mPQIhUpK4s4MNJ3T-h1P3oXj4lKijS-oojq46Rq34fg0TwuwZm-LUjHgvRdQdG-vU8cqw6bR_nQSARnE_hjWzz8P0lfnX-fIv8Bo6KXqg</recordid><startdate>202008</startdate><enddate>202008</enddate><creator>Bachoud‐Lévi, Anne‐Catherine</creator><creator>Schramm, Catherine</creator><creator>Remy, Philippe</creator><creator>Aubin, Ghislaine</creator><creator>Blond, Serge</creator><creator>Bocket, Laurence</creator><creator>Brugières, Pierre</creator><creator>Calvas, Fabienne</creator><creator>Calvier, Elisabeth</creator><creator>Cassim, François</creator><creator>Challine, Dominique</creator><creator>Gagou, Clarisse Scherer</creator><creator>Langavant, Laurent Cleret</creator><creator>Collier, Francis</creator><creator>Cottencin, Olivier</creator><creator>David, Philippe</creator><creator>Damier, Philippe</creator><creator>Delliaux, Marie</creator><creator>Delmaire, Christine</creator><creator>Delval, Arnaud</creator><creator>Démonet, Jean‐François</creator><creator>Descamps, Philippe</creator><creator>Gaura, Véronique</creator><creator>Gohier, Bénédicte</creator><creator>Goldman, Serge</creator><creator>Haddad, Bassam</creator><creator>Izopet, Jacques</creator><creator>Jeny, Roland</creator><creator>Kerr‐Conte, Julie</creator><creator>Krystowiak, Pierre</creator><creator>Lalanne, Christophe</creator><creator>Lavisse, Sonia</creator><creator>Lefaucheur, Jean‐Pascal</creator><creator>Lemoine, Laurie</creator><creator>Levivier, Marc</creator><creator>Lotterie, Jean‐Albert</creator><creator>Lunel‐Fabiani, Françoise</creator><creator>Maison, Patrick</creator><creator>Massager, Nicolas</creator><creator>Massart, Renaud</creator><creator>Menei, Philippe</creator><creator>Montero‐Menei, Claudia</creator><creator>Neveu, Isabelle</creator><creator>Parant, Olivier</creator><creator>Pautot, Vivien</creator><creator>Payoux, Pierre</creator><creator>Pereon, Yann</creator><creator>Rialland, Amandine</creator><creator>Rosser, Anne</creator><creator>Rouard, Hélène</creator><creator>Schmitz, David</creator><creator>Simonetta‐Moreau, Marion</creator><creator>Simonin, Clémence</creator><creator>Slama, Hichem</creator><creator>Sol, Jean‐Christophe</creator><creator>Supiot, Frédéric</creator><creator>Tanguy, Jean‐Yves</creator><creator>Tenenbaum, Liliane</creator><creator>Verny, Christophe</creator><creator>Youssov, Katia</creator><creator>Peschanski, Marc</creator><creator>Audureau, Etienne</creator><creator>Palfi, Stéphane</creator><creator>Hantraye, Philippe</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><general>Wiley</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0003-3000-2210</orcidid></search><sort><creationdate>202008</creationdate><title>Human Fetal Cell Therapy in Huntington's Disease: A Randomized, Multicenter, Phase II Trial</title><author>Bachoud‐Lévi, Anne‐Catherine ; Schramm, Catherine ; Remy, Philippe ; Aubin, Ghislaine ; Blond, Serge ; Bocket, Laurence ; Brugières, Pierre ; Calvas, Fabienne ; Calvier, Elisabeth ; Cassim, François ; Challine, Dominique ; Gagou, Clarisse Scherer ; Langavant, Laurent Cleret ; Collier, Francis ; Cottencin, Olivier ; David, Philippe ; Damier, Philippe ; Delliaux, Marie ; Delmaire, Christine ; Delval, Arnaud ; Démonet, Jean‐François ; Descamps, Philippe ; Gaura, Véronique ; Gohier, Bénédicte ; Goldman, Serge ; Haddad, Bassam ; Izopet, Jacques ; Jeny, Roland ; Kerr‐Conte, Julie ; Krystowiak, Pierre ; Lalanne, Christophe ; Lavisse, Sonia ; Lefaucheur, Jean‐Pascal ; Lemoine, Laurie ; Levivier, Marc ; Lotterie, Jean‐Albert ; Lunel‐Fabiani, Françoise ; Maison, Patrick ; Massager, Nicolas ; Massart, Renaud ; Menei, Philippe ; Montero‐Menei, Claudia ; Neveu, Isabelle ; Parant, Olivier ; Pautot, Vivien ; Payoux, Pierre ; Pereon, Yann ; Rialland, Amandine ; Rosser, Anne ; Rouard, Hélène ; Schmitz, David ; Simonetta‐Moreau, Marion ; Simonin, Clémence ; Slama, Hichem ; Sol, Jean‐Christophe ; Supiot, Frédéric ; Tanguy, Jean‐Yves ; Tenenbaum, Liliane ; Verny, Christophe ; Youssov, Katia ; Peschanski, Marc ; Audureau, Etienne ; Palfi, Stéphane ; Hantraye, Philippe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3401-e042e0b8afeedfcaa8630642f7b599ff3a3f88940db626848bda2a1bb791a7cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Cell therapy</topic><topic>Cell- and Tissue-Based Therapy</topic><topic>Cellular Biology</topic><topic>Fetuses</topic><topic>Graft rejection</topic><topic>Humans</topic><topic>Huntington Disease - therapy</topic><topic>Huntington's disease</topic><topic>Huntingtons disease</topic><topic>Leukocytes</topic><topic>Life Sciences</topic><topic>MIG‐HD</topic><topic>Motor task performance</topic><topic>Movement disorders</topic><topic>Neurodegenerative Diseases</topic><topic>Patients</topic><topic>phase 2 trial</topic><topic>Transplantation</topic><topic>Transplants & implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bachoud‐Lévi, Anne‐Catherine</creatorcontrib><creatorcontrib>Schramm, Catherine</creatorcontrib><creatorcontrib>Remy, Philippe</creatorcontrib><creatorcontrib>Aubin, Ghislaine</creatorcontrib><creatorcontrib>Blond, Serge</creatorcontrib><creatorcontrib>Bocket, Laurence</creatorcontrib><creatorcontrib>Brugières, Pierre</creatorcontrib><creatorcontrib>Calvas, Fabienne</creatorcontrib><creatorcontrib>Calvier, Elisabeth</creatorcontrib><creatorcontrib>Cassim, François</creatorcontrib><creatorcontrib>Challine, Dominique</creatorcontrib><creatorcontrib>Gagou, Clarisse Scherer</creatorcontrib><creatorcontrib>Langavant, Laurent Cleret</creatorcontrib><creatorcontrib>Collier, Francis</creatorcontrib><creatorcontrib>Cottencin, Olivier</creatorcontrib><creatorcontrib>David, Philippe</creatorcontrib><creatorcontrib>Damier, Philippe</creatorcontrib><creatorcontrib>Delliaux, Marie</creatorcontrib><creatorcontrib>Delmaire, Christine</creatorcontrib><creatorcontrib>Delval, Arnaud</creatorcontrib><creatorcontrib>Démonet, Jean‐François</creatorcontrib><creatorcontrib>Descamps, Philippe</creatorcontrib><creatorcontrib>Gaura, Véronique</creatorcontrib><creatorcontrib>Gohier, Bénédicte</creatorcontrib><creatorcontrib>Goldman, Serge</creatorcontrib><creatorcontrib>Haddad, Bassam</creatorcontrib><creatorcontrib>Izopet, Jacques</creatorcontrib><creatorcontrib>Jeny, Roland</creatorcontrib><creatorcontrib>Kerr‐Conte, Julie</creatorcontrib><creatorcontrib>Krystowiak, Pierre</creatorcontrib><creatorcontrib>Lalanne, Christophe</creatorcontrib><creatorcontrib>Lavisse, Sonia</creatorcontrib><creatorcontrib>Lefaucheur, Jean‐Pascal</creatorcontrib><creatorcontrib>Lemoine, Laurie</creatorcontrib><creatorcontrib>Levivier, Marc</creatorcontrib><creatorcontrib>Lotterie, Jean‐Albert</creatorcontrib><creatorcontrib>Lunel‐Fabiani, Françoise</creatorcontrib><creatorcontrib>Maison, Patrick</creatorcontrib><creatorcontrib>Massager, Nicolas</creatorcontrib><creatorcontrib>Massart, Renaud</creatorcontrib><creatorcontrib>Menei, Philippe</creatorcontrib><creatorcontrib>Montero‐Menei, Claudia</creatorcontrib><creatorcontrib>Neveu, Isabelle</creatorcontrib><creatorcontrib>Parant, Olivier</creatorcontrib><creatorcontrib>Pautot, Vivien</creatorcontrib><creatorcontrib>Payoux, Pierre</creatorcontrib><creatorcontrib>Pereon, Yann</creatorcontrib><creatorcontrib>Rialland, Amandine</creatorcontrib><creatorcontrib>Rosser, Anne</creatorcontrib><creatorcontrib>Rouard, Hélène</creatorcontrib><creatorcontrib>Schmitz, David</creatorcontrib><creatorcontrib>Simonetta‐Moreau, Marion</creatorcontrib><creatorcontrib>Simonin, Clémence</creatorcontrib><creatorcontrib>Slama, Hichem</creatorcontrib><creatorcontrib>Sol, Jean‐Christophe</creatorcontrib><creatorcontrib>Supiot, Frédéric</creatorcontrib><creatorcontrib>Tanguy, Jean‐Yves</creatorcontrib><creatorcontrib>Tenenbaum, Liliane</creatorcontrib><creatorcontrib>Verny, Christophe</creatorcontrib><creatorcontrib>Youssov, Katia</creatorcontrib><creatorcontrib>Peschanski, Marc</creatorcontrib><creatorcontrib>Audureau, Etienne</creatorcontrib><creatorcontrib>Palfi, Stéphane</creatorcontrib><creatorcontrib>Hantraye, Philippe</creatorcontrib><creatorcontrib>on behalf the Multicentric Intracerebral Grafting in Huntington's Disease Group</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Movement disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bachoud‐Lévi, Anne‐Catherine</au><au>Schramm, Catherine</au><au>Remy, Philippe</au><au>Aubin, Ghislaine</au><au>Blond, Serge</au><au>Bocket, Laurence</au><au>Brugières, Pierre</au><au>Calvas, Fabienne</au><au>Calvier, Elisabeth</au><au>Cassim, François</au><au>Challine, Dominique</au><au>Gagou, Clarisse Scherer</au><au>Langavant, Laurent Cleret</au><au>Collier, Francis</au><au>Cottencin, Olivier</au><au>David, Philippe</au><au>Damier, Philippe</au><au>Delliaux, Marie</au><au>Delmaire, Christine</au><au>Delval, Arnaud</au><au>Démonet, Jean‐François</au><au>Descamps, Philippe</au><au>Gaura, Véronique</au><au>Gohier, Bénédicte</au><au>Goldman, Serge</au><au>Haddad, Bassam</au><au>Izopet, Jacques</au><au>Jeny, Roland</au><au>Kerr‐Conte, Julie</au><au>Krystowiak, Pierre</au><au>Lalanne, Christophe</au><au>Lavisse, Sonia</au><au>Lefaucheur, Jean‐Pascal</au><au>Lemoine, Laurie</au><au>Levivier, Marc</au><au>Lotterie, Jean‐Albert</au><au>Lunel‐Fabiani, Françoise</au><au>Maison, Patrick</au><au>Massager, Nicolas</au><au>Massart, Renaud</au><au>Menei, Philippe</au><au>Montero‐Menei, Claudia</au><au>Neveu, Isabelle</au><au>Parant, Olivier</au><au>Pautot, Vivien</au><au>Payoux, Pierre</au><au>Pereon, Yann</au><au>Rialland, Amandine</au><au>Rosser, Anne</au><au>Rouard, Hélène</au><au>Schmitz, David</au><au>Simonetta‐Moreau, Marion</au><au>Simonin, Clémence</au><au>Slama, Hichem</au><au>Sol, Jean‐Christophe</au><au>Supiot, Frédéric</au><au>Tanguy, Jean‐Yves</au><au>Tenenbaum, Liliane</au><au>Verny, Christophe</au><au>Youssov, Katia</au><au>Peschanski, Marc</au><au>Audureau, Etienne</au><au>Palfi, Stéphane</au><au>Hantraye, Philippe</au><aucorp>on behalf the Multicentric Intracerebral Grafting in Huntington's Disease Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human Fetal Cell Therapy in Huntington's Disease: A Randomized, Multicenter, Phase II Trial</atitle><jtitle>Movement disorders</jtitle><addtitle>Mov Disord</addtitle><date>2020-08</date><risdate>2020</risdate><volume>35</volume><issue>8</issue><spage>1323</spage><epage>1335</epage><pages>1323-1335</pages><issn>0885-3185</issn><eissn>1531-8257</eissn><abstract>Background
Huntington's disease is a rare, severe, inherited neurodegenerative disease in which we assessed the safety and efficacy of grafting human fetal ganglionic eminence intrastriatally.
Methods
Patients at the early stage of the disease were enrolled in the Multicentric Intracerebral Grafting in Huntington's Disease trial, a delayed‐start phase II randomized study. After a run‐in period of 12 months, patients were randomized at month 12 to either the treatment group (transplanted at month 13–month 14) or the control group and secondarily treated 20 months later (month 33–month 34). The primary outcome was total motor score compared between both groups 20 months postrandomization (month 32). Secondary outcomes included clinical, imaging, and electrophysiological findings and a comparison of pregraft and postgraft total motor score slopes during the entire study period (month 0–month 52) regardless of the time of transplant.
Results
Of 54 randomized patients, 45 were transplanted; 26 immediately (treatment) and 19 delayed (control). Mean total motor score at month 32 did not differ between groups (treated controls difference in means adjusted for M12: +2.9 [95% confidence interval, −2.8 to 8.6]; P = 0.31). Its rate of decline after transplantation was similar to that before transplantation. A total of 27 severe adverse events were recorded in the randomized patients, 10 of which were related to the transplant procedure. Improvement of procedures during the trial significantly decreased the frequency of surgical events.We found antihuman leucocytes antigen antibodies in 40% of the patients.
Conclusion
No clinical benefit was found in this trial. This may have been related to graft rejection. Ectopia and high track number negatively influence the graft outcome. Procedural adjustments substantially improved surgical safety. (ClinicalTrials.gov NCT00190450.) © 2020 International Parkinson and Movement Disorder Society</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>32666599</pmid><doi>10.1002/mds.28201</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-3000-2210</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0885-3185 |
| ispartof | Movement disorders, 2020-08, Vol.35 (8), p.1323-1335 |
| issn | 0885-3185 1531-8257 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_inserm_03549919v1 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Cell therapy Cell- and Tissue-Based Therapy Cellular Biology Fetuses Graft rejection Humans Huntington Disease - therapy Huntington's disease Huntingtons disease Leukocytes Life Sciences MIG‐HD Motor task performance Movement disorders Neurodegenerative Diseases Patients phase 2 trial Transplantation Transplants & implants |
| title | Human Fetal Cell Therapy in Huntington's Disease: A Randomized, Multicenter, Phase II Trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T02%3A26%3A10IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Human%20Fetal%20Cell%20Therapy%20in%20Huntington's%20Disease:%20A%20Randomized,%20Multicenter,%20Phase%20II%20Trial&rft.jtitle=Movement%20disorders&rft.au=Bachoud%E2%80%90L%C3%A9vi,%20Anne%E2%80%90Catherine&rft.aucorp=on%20behalf%20the%20Multicentric%20Intracerebral%20Grafting%20in%20Huntington's%20Disease%20Group&rft.date=2020-08&rft.volume=35&rft.issue=8&rft.spage=1323&rft.epage=1335&rft.pages=1323-1335&rft.issn=0885-3185&rft.eissn=1531-8257&rft_id=info:doi/10.1002/mds.28201&rft_dat=%3Cproquest_hal_p%3E2432444477%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2432444477&rft_id=info:pmid/32666599&rfr_iscdi=true |