Direct brain infusion of glial cell line–derived neurotrophic factor in Parkinson disease
Glial cell line–derived neurotrophic factor (GDNF) is a potent neurotrophic factor with restorative effects in a wide variety of rodent and primate models of Parkinson disease, but penetration into brain tissue from either the blood or the cerebro-spinal fluid is limited. Here we delivered GDNF dire...
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| Veröffentlicht in: | Nature medicine 2003-05, Vol.9 (5), p.589-595 |
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| creator | Gill, Steven S. Patel, Nikunj K. Hotton, Gary R. O'Sullivan, Karen McCarter, Renée Bunnage, Martin Brooks, David J. Svendsen, Clive N. Heywood, Peter |
| description | Glial cell line–derived neurotrophic factor (GDNF) is a potent neurotrophic factor with restorative effects in a wide variety of rodent and primate models of Parkinson disease, but penetration into brain tissue from either the blood or the cerebro-spinal fluid is limited. Here we delivered GDNF directly into the putamen of five Parkinson patients in a phase 1 safety trial. One catheter needed to be repositioned and there were changes in the magnetic resonance images that disappeared after lowering the concentration of GDNF. After one year, there were no serious clinical side effects, a 39% improvement in the off-medication motor sub-score of the Unified Parkinson's Disease Rating Scale (UPDRS) and a 61% improvement in the activities of daily living sub-score. Medication-induced dyskinesias were reduced by 64% and were not observed off medication during chronic GDNF delivery. Positron emission tomography (PET) scans of [
18
F]dopamine uptake showed a significant 28% increase in putamen dopamine storage after 18 months, suggesting a direct effect of GDNF on dopamine function. This study warrants careful examination of GDNF as a treatment for Parkinson disease. |
| doi_str_mv | 10.1038/nm850 |
| format | Article |
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18
F]dopamine uptake showed a significant 28% increase in putamen dopamine storage after 18 months, suggesting a direct effect of GDNF on dopamine function. This study warrants careful examination of GDNF as a treatment for Parkinson disease.</description><identifier>ISSN: 1078-8956</identifier><identifier>EISSN: 1546-170X</identifier><identifier>DOI: 10.1038/nm850</identifier><identifier>PMID: 12669033</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Biomedical and Life Sciences ; Biomedicine ; Blood ; Cancer Research ; Dihydroxyphenylalanine - metabolism ; Drugs ; Emissions ; Fluorine Radioisotopes ; Glial Cell Line-Derived Neurotrophic Factor ; Humans ; Infectious Diseases ; Medical instruments ; Metabolic Diseases ; Middle Aged ; Molecular Medicine ; Nerve Growth Factors - administration & dosage ; Neurosciences ; Parkinson Disease - drug therapy ; Parkinson's disease ; Pilot Projects ; Putamen - drug effects ; Research Design ; Rodents ; Side effects ; Tomography, Emission-Computed</subject><ispartof>Nature medicine, 2003-05, Vol.9 (5), p.589-595</ispartof><rights>Springer Nature America, Inc. 2003</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c604t-7a5d8d60f54d206c248315358796f075ae4ea7bdf4e5a04881c25bf502ba29443</citedby><cites>FETCH-LOGICAL-c604t-7a5d8d60f54d206c248315358796f075ae4ea7bdf4e5a04881c25bf502ba29443</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nm850$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nm850$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12669033$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gill, Steven S.</creatorcontrib><creatorcontrib>Patel, Nikunj K.</creatorcontrib><creatorcontrib>Hotton, Gary R.</creatorcontrib><creatorcontrib>O'Sullivan, Karen</creatorcontrib><creatorcontrib>McCarter, Renée</creatorcontrib><creatorcontrib>Bunnage, Martin</creatorcontrib><creatorcontrib>Brooks, David J.</creatorcontrib><creatorcontrib>Svendsen, Clive N.</creatorcontrib><creatorcontrib>Heywood, Peter</creatorcontrib><title>Direct brain infusion of glial cell line–derived neurotrophic factor in Parkinson disease</title><title>Nature medicine</title><addtitle>Nat Med</addtitle><addtitle>Nat Med</addtitle><description>Glial cell line–derived neurotrophic factor (GDNF) is a potent neurotrophic factor with restorative effects in a wide variety of rodent and primate models of Parkinson disease, but penetration into brain tissue from either the blood or the cerebro-spinal fluid is limited. Here we delivered GDNF directly into the putamen of five Parkinson patients in a phase 1 safety trial. One catheter needed to be repositioned and there were changes in the magnetic resonance images that disappeared after lowering the concentration of GDNF. After one year, there were no serious clinical side effects, a 39% improvement in the off-medication motor sub-score of the Unified Parkinson's Disease Rating Scale (UPDRS) and a 61% improvement in the activities of daily living sub-score. Medication-induced dyskinesias were reduced by 64% and were not observed off medication during chronic GDNF delivery. Positron emission tomography (PET) scans of [
18
F]dopamine uptake showed a significant 28% increase in putamen dopamine storage after 18 months, suggesting a direct effect of GDNF on dopamine function. This study warrants careful examination of GDNF as a treatment for Parkinson disease.</description><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood</subject><subject>Cancer Research</subject><subject>Dihydroxyphenylalanine - metabolism</subject><subject>Drugs</subject><subject>Emissions</subject><subject>Fluorine Radioisotopes</subject><subject>Glial Cell Line-Derived Neurotrophic Factor</subject><subject>Humans</subject><subject>Infectious Diseases</subject><subject>Medical instruments</subject><subject>Metabolic Diseases</subject><subject>Middle Aged</subject><subject>Molecular Medicine</subject><subject>Nerve Growth Factors - administration & dosage</subject><subject>Neurosciences</subject><subject>Parkinson Disease - drug therapy</subject><subject>Parkinson's disease</subject><subject>Pilot Projects</subject><subject>Putamen - drug effects</subject><subject>Research Design</subject><subject>Rodents</subject><subject>Side effects</subject><subject>Tomography, Emission-Computed</subject><issn>1078-8956</issn><issn>1546-170X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN0t1qFDEUAOBBFFtrX0EGwYIXU_M_mctSqy0UKv4heDFkMiezqZlkTWaK3vUd-oZ9ElN3YV0pKLlISL6Tn5NTFPsYHWJE5Ss_So4eFLuYM1HhGn15mMeolpVsuNgpnqR0iRCiiDePix1MhGgQpbvF19c2gp7KLirrS-vNnGzwZTDl4KxypQbnSmc93F7f9BDtFfSlhzmGKYblwurSKD2FmCPLdyp-sz7l6N4mUAmeFo-Mcgn21_1e8enNycfj0-r84u3Z8dF5pQViU1Ur3steIMNZT5DQhEmKOeWyboRBNVfAQNVdbxhwhZiUWBPeGY5Ip0jDGN0rDlb7LmP4PkOa2tGmu4srD2FObU0JQVjKf0Isa8EIFRk-_wtehjn6_IiWEIoxF5hkVK3QoBy0OXU5J0oP4CEqFzwYm6ePcENlIwlqsj-8x-fWw2j1vQEvtwKymeDHNKg5pfbsw_v_txeft-3BH3YByk2LFNw85Z9P2_DFCuoYUopg2mW0o4o_W4zau6prf1ddds_W6Zq7EfqNWpfZ5sSUl_wAcZPP7Z1-ARYL20M</recordid><startdate>20030501</startdate><enddate>20030501</enddate><creator>Gill, Steven S.</creator><creator>Patel, Nikunj K.</creator><creator>Hotton, Gary R.</creator><creator>O'Sullivan, Karen</creator><creator>McCarter, Renée</creator><creator>Bunnage, Martin</creator><creator>Brooks, David J.</creator><creator>Svendsen, Clive N.</creator><creator>Heywood, Peter</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20030501</creationdate><title>Direct brain infusion of glial cell line–derived neurotrophic factor in Parkinson disease</title><author>Gill, Steven S. ; Patel, Nikunj K. ; Hotton, Gary R. ; O'Sullivan, Karen ; McCarter, Renée ; Bunnage, Martin ; Brooks, David J. ; Svendsen, Clive N. ; Heywood, Peter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c604t-7a5d8d60f54d206c248315358796f075ae4ea7bdf4e5a04881c25bf502ba29443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Blood</topic><topic>Cancer Research</topic><topic>Dihydroxyphenylalanine - metabolism</topic><topic>Drugs</topic><topic>Emissions</topic><topic>Fluorine Radioisotopes</topic><topic>Glial Cell Line-Derived Neurotrophic Factor</topic><topic>Humans</topic><topic>Infectious Diseases</topic><topic>Medical instruments</topic><topic>Metabolic Diseases</topic><topic>Middle Aged</topic><topic>Molecular Medicine</topic><topic>Nerve Growth Factors - administration & dosage</topic><topic>Neurosciences</topic><topic>Parkinson Disease - drug therapy</topic><topic>Parkinson's disease</topic><topic>Pilot Projects</topic><topic>Putamen - drug effects</topic><topic>Research Design</topic><topic>Rodents</topic><topic>Side effects</topic><topic>Tomography, Emission-Computed</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gill, Steven S.</creatorcontrib><creatorcontrib>Patel, Nikunj K.</creatorcontrib><creatorcontrib>Hotton, Gary R.</creatorcontrib><creatorcontrib>O'Sullivan, Karen</creatorcontrib><creatorcontrib>McCarter, Renée</creatorcontrib><creatorcontrib>Bunnage, Martin</creatorcontrib><creatorcontrib>Brooks, David J.</creatorcontrib><creatorcontrib>Svendsen, Clive N.</creatorcontrib><creatorcontrib>Heywood, Peter</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gill, Steven S.</au><au>Patel, Nikunj K.</au><au>Hotton, Gary R.</au><au>O'Sullivan, Karen</au><au>McCarter, Renée</au><au>Bunnage, Martin</au><au>Brooks, David J.</au><au>Svendsen, Clive N.</au><au>Heywood, Peter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Direct brain infusion of glial cell line–derived neurotrophic factor in Parkinson disease</atitle><jtitle>Nature medicine</jtitle><stitle>Nat Med</stitle><addtitle>Nat Med</addtitle><date>2003-05-01</date><risdate>2003</risdate><volume>9</volume><issue>5</issue><spage>589</spage><epage>595</epage><pages>589-595</pages><issn>1078-8956</issn><eissn>1546-170X</eissn><abstract>Glial cell line–derived neurotrophic factor (GDNF) is a potent neurotrophic factor with restorative effects in a wide variety of rodent and primate models of Parkinson disease, but penetration into brain tissue from either the blood or the cerebro-spinal fluid is limited. Here we delivered GDNF directly into the putamen of five Parkinson patients in a phase 1 safety trial. One catheter needed to be repositioned and there were changes in the magnetic resonance images that disappeared after lowering the concentration of GDNF. After one year, there were no serious clinical side effects, a 39% improvement in the off-medication motor sub-score of the Unified Parkinson's Disease Rating Scale (UPDRS) and a 61% improvement in the activities of daily living sub-score. Medication-induced dyskinesias were reduced by 64% and were not observed off medication during chronic GDNF delivery. Positron emission tomography (PET) scans of [
18
F]dopamine uptake showed a significant 28% increase in putamen dopamine storage after 18 months, suggesting a direct effect of GDNF on dopamine function. This study warrants careful examination of GDNF as a treatment for Parkinson disease.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>12669033</pmid><doi>10.1038/nm850</doi><tpages>7</tpages></addata></record> |
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| subjects | Biomedical and Life Sciences Biomedicine Blood Cancer Research Dihydroxyphenylalanine - metabolism Drugs Emissions Fluorine Radioisotopes Glial Cell Line-Derived Neurotrophic Factor Humans Infectious Diseases Medical instruments Metabolic Diseases Middle Aged Molecular Medicine Nerve Growth Factors - administration & dosage Neurosciences Parkinson Disease - drug therapy Parkinson's disease Pilot Projects Putamen - drug effects Research Design Rodents Side effects Tomography, Emission-Computed |
| title | Direct brain infusion of glial cell line–derived neurotrophic factor in Parkinson disease |
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