{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:41:25Z","timestamp":1790336485703,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,11,18]],"date-time":"2010-11-18T00:00:00Z","timestamp":1290038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: AAV2\u2010neurturin (CERE\u2010120) is designed to deliver the neurotrophic\u2010factor, neurturin, to the striatum to restore and protect degenerating nigrostriatal neurons in Parkinson's disease (PD). A common hypothesis is that following expression in the striatum, neurotrophic\u2010factors like neurturin (NRTN) will be transported from degenerating terminals to their cell bodies in the substantia nigra pars compacta (SNc). Methods: We tested this concept using immunohistochemistry, comparing the bioactivity of AAV2\u2010neurturin in brains of PD patients versus those of nonhuman primates similarly treated. Results: NRTN\u2010immunostaining in the targeted striatum was seen in all PD cases (mean putaminal coverage: \u223c15% by volume); comparable expression was observed in young, aged, and parkinsonian monkeys. In the SNc cell bodies, however, only rare evidence of neurturin was seen in PD, while ample evidence of intense nigral\u2010NRTN was observed in all monkeys. NRTN\u2010expression was associated with occasional, sparse TH\u2010induction in the striatum of PD, but nothing apparent in the SNc. In primates, NRTN produced robust TH\u2010induction throughout the nigrostriatal neurons. Discussion: These data provide the first evidence that gene therapy can increase expression of a neurotrophic\u2010factor deep in the PD brain and that clear but modest enhancement of degenerating neurons can be induced. They also provide important insight regarding deficiencies in the status of nigrostriatal neurons in advanced PD, suggesting that serious axon\u2010transport deficits reduced the bioactivity of AAV2\u2010NRTN by limiting the protein exposed to the cell body. Thus, future efforts using neurotrophic\u2010factors to treat neurodegenerative diseases will need to target both the terminal fields and the cell bodies of degenerating neurons to assure maximal benefit is achieved. \u00a9 2010 Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.23442","type":"journal-article","created":{"date-parts":[[2010,11,18]],"date-time":"2010-11-18T11:01:29Z","timestamp":1290078089000},"page":"27-36","source":"Crossref","is-referenced-by-count":151,"title":["Bioactivity of AAV2\u2010neurturin gene therapy (CERE\u2010120): Differences between Parkinson's disease and nonhuman primate brains"],"prefix":"10.1002","volume":"26","author":[{"given":"Raymond T.","family":"Bartus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Herzog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamar","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joao","family":"Siffert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Eugene M.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Warren","family":"Olanow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliott J.","family":"Mufson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey H.","family":"Kordower","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,11,18]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0730070.x"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-13-04929.1998"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5492.767"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21032"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199909)46:3<419::AID-ANA21>3.0.CO;2-Q"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.60.1.69"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20737"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2006.07.015"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20861"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.04.003"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300010"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21503"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.170"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000340682.06068.01"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1353-8020(08)70052-X"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70065-6"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70254-4"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1159\/000017069"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1175"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1997.0151"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-12-04686.2000"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(98)00059-8"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(94)90099-X"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10689"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2009.103"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/373335a0"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00274.x"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1998.6887"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/380252a0"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1353-8020(09)70829-6"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2000.7397"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.227061"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5427-08.2009"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-004-0952-x"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3463-09.2009"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(99)00208-6"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.31.061307.090711"}],"container-title":["Movement 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