{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:08:48Z","timestamp":1779296928077,"version":"3.51.4"},"reference-count":20,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:sec>\n<jats:title>Object<\/jats:title>\n<jats:p>The authors describe the first clinical trial with encapsulated cell biodelivery (ECB) implants that deliver nerve growth factor (NGF) to the cholinergic basal forebrain with the intention of halting the degeneration of cholinergic neurons and the associated cognitive decline in patients with Alzheimer disease (AD). The NsG0202 implant (NsGene A\/S) consists of an NGF-producing, genetically engineered human cell line encapsulated behind a semipermeable hollow fiber membrane that allows the influx of nutrients and the efflux of NGF. The centimeter-long capsule is attached to an inert polymer tether that is used to guide the capsule to the target via stereotactic techniques and is anchored to the skull at the bur hole.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Six patients with mild to moderate AD were included in this Phase Ib open-label safety study and were divided into 2 dose cohorts. The first cohort of 3 patients received single implants targeting the basal nucleus of Meynert (Ch4 region) bilaterally (2 implants per patient), and after a safety evaluation, a second cohort of 3 patients received bilateral implants (a total of 4 implants per patient) targeting both the Ch4 region and the vertical limb of the diagonal band of Broca (Ch2 region). Stereotactic implantation of the devices was successfully accomplished in all patients. Despite extensive brain atrophy, all targets could be reached without traversing sulci, the insula, or lateral ventricles.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Postoperative CT scans allowed visualization of the barium-impregnated tethers, and fusion of the scans with stereotactic MR images scan was used to verify the intended positions of the implants. Follow-up MRI at 3 and 12 months postimplantation showed no evidence of inflammation or device displacement. At 12 months, implants were successfully retrieved, and low but persistent NGF secretion was detected in half of the patients.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>With refinement, the ECB technology is positioned to become an important therapeutic platform in restorative neurosurgery and, in combination with other therapeutic factors, may be relevant for the treatment of a variety of neurological disorders. Clinical trial registration no.: NCT01163825.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2012.2.jns11714","type":"journal-article","created":{"date-parts":[[2012,6,1]],"date-time":"2012-06-01T13:57:23Z","timestamp":1338559043000},"page":"340-347","source":"Crossref","is-referenced-by-count":109,"title":["Targeted delivery of nerve growth factor via encapsulated cell biodelivery in Alzheimer disease: a technology platform for restorative neurosurgery"],"prefix":"10.3171","volume":"117","author":[{"given":"Lars U.","family":"Wahlberg","sequence":"first","affiliation":[{"name":"Geriatric Medicine,"},{"name":"NsGene A\/S, Ballerup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00f6ran","family":"Lind","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per M.","family":"Almqvist","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery,"},{"name":"NsGene A\/S, Ballerup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Kusk","sequence":"additional","affiliation":[{"name":"NsGene A\/S, Ballerup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Torn\u00f8e","sequence":"additional","affiliation":[{"name":"NsGene A\/S, Ballerup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bengt","family":"Juliusson","sequence":"additional","affiliation":[{"name":"NsGene A\/S, Ballerup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"S\u00f6derman","sequence":"additional","affiliation":[{"name":"Neuroradiology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Selld\u00e9n","sequence":"additional","affiliation":[{"name":"Anesthesiology, Karolinska University Hospital, Stockholm, Sweden; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c5ke","family":"Seiger","sequence":"additional","affiliation":[{"name":"Geriatric Medicine,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Eriksdotter-J\u00f6nhagen","sequence":"additional","affiliation":[{"name":"Geriatric Medicine,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bengt","family":"Linderoth","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery,"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1754","reference":[{"key":"b1-jns11714","series-title":"Proc Natl Acad Sci U S A","first-page":"10439","article-title":"Failed retrograde transport of NGF in a mouse model of Down's syndrome: reversal of cholinergic neurodegenerative phenotypes following NGF infusion","volume":"98","author":"Cooper","year":"2001"},{"key":"b2-jns11714","series-title":"Dement Geriatr Cogn Disord","article-title":"Encapsulated cell biodelivery of NGF to the basal forebrain of Alzheimer patients","author":"Eriksdotter-J\u00f6nhagen","year":"2012"},{"key":"b3-jns11714","series-title":"Dement Geriatr Cogn Disord","first-page":"246","article-title":"Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer's disease","volume":"9","author":"Eriksdotter J\u00f6nhagen","year":"1998"},{"key":"b4-jns11714","series-title":"Neurotherapeutics","first-page":"123","article-title":"Image-guided convection-enhanced delivery platform in the treatment of neurological diseases","volume":"5","author":"Fiandaca","year":"2008"},{"key":"b5-jns11714","series-title":"Gene Ther","article-title":"Increased encapsulated cell biodelivery of nerve growth factor in the brain by transposon-mediated gene transfer","author":"Fjord-Larsen","year":"2011"},{"key":"b6-jns11714","series-title":"Mol Ther","first-page":"2164","article-title":"Long-term delivery of nerve growth factor by encapsulated cell biodelivery in the G\u00f6ttingen minipig basal forebrain","volume":"18","author":"Fjord-Larsen","year":"2010"},{"key":"b7-jns11714","series-title":"J Psychiatr Res","first-page":"189","article-title":"\u201cMini-mental state\u201d. A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975"},{"key":"b8-jns11714","series-title":"Neurobiol Aging","first-page":"75","article-title":"Localization of nerve growth factor receptors in the normal human brain and in Alzheimer's disease","volume":"10","author":"Hefti","year":"1989"},{"key":"b9-jns11714","series-title":"Lancet Neurol","first-page":"309","article-title":"AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial","volume":"10","author":"LeWitt","year":"2011"},{"key":"b10-jns11714","series-title":"Cell Transplant","first-page":"205","article-title":"Effects of intraventricular encapsulated hNGF-secreting fibroblasts in aged rats","volume":"5","author":"Lindner","year":"1996"},{"key":"b11-jns11714","series-title":"Exp Neurol","first-page":"82","article-title":"Encapsulated cell biodelivery of GDNF: a novel clinical strategy for neuroprotection and neuroregeneration in Parkinson's disease?","volume":"209","author":"Lindvall","year":"2008"},{"key":"b12-jns11714","series-title":"Atlas of the Human Brain","year":"2008"},{"key":"b13-jns11714","series-title":"Neurology","first-page":"939","article-title":"Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease","volume":"34","author":"McKhann","year":"1984"},{"key":"b14-jns11714","series-title":"Exp Neurol","first-page":"153","article-title":"Long-term reversal of cholinergic neuronal decline in aged non-human primates by lentiviral NGF gene delivery","volume":"215","author":"Nagahara","year":"2009"},{"key":"b15-jns11714","series-title":"Behav Brain Res","first-page":"515","article-title":"The cholinergic system, nerve growth factor and the cytoskeleton","volume":"221","author":"Niewiadomska","year":"2011"},{"issue":"1 Suppl 1","key":"b16-jns11714","series-title":"J Neurol","first-page":"S12","article-title":"Role of growth factors in degeneration and regeneration in the central nervous system; clinical experiences with NGF in Parkinson's and Alzheimer's diseases","volume":"242","author":"Olson","year":"1994"},{"key":"b17-jns11714","series-title":"J Neural Transm","first-page":"323","article-title":"Alzheimer's disease and NGF signaling","volume":"111","author":"Salehi","year":"2004"},{"key":"b18-jns11714","series-title":"Nat Med","first-page":"551","article-title":"A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease","volume":"11","author":"Tuszynski","year":"2005"},{"key":"b19-jns11714","series-title":"Proc Natl Acad Sci U S A","first-page":"2324","article-title":"Polymer-encapsulated cells genetically modified to secrete human nerve growth factor promote the survival of axotomized septal cholinergic neurons","volume":"91","author":"Winn","year":"1994"},{"key":"b20-jns11714","series-title":"Exp Neurol","first-page":"126","article-title":"Polymer-encapsulated genetically modified cells continue to secrete human nerve growth factor for over one year in rat ventricles: behavioral and anatomical consequences","volume":"140","author":"Winn","year":"1996"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/117\/2\/article-p340.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/117\/2\/article-p340.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/117\/2\/article-p340.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,26]],"date-time":"2023-03-26T23:20:27Z","timestamp":1679872827000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/117\/2\/article-p340.xml"}},"subtitle":["Clinical article"],"short-title":[],"issued":{"date-parts":[[2012,8]]},"references-count":20,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3171\/2012.2.jns11714","relation":{},"ISSN":["0022-3085","1933-0693"],"issn-type":[{"value":"0022-3085","type":"print"},{"value":"1933-0693","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,8]]}}}