{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T02:13:18Z","timestamp":1776219198225,"version":"3.50.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T00:00:00Z","timestamp":1601337600000},"content-version":"vor","delay-in-days":272,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Newron Sweden AB"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We studied the feasibility, safety, tolerability and pharmacokinetics of intracerebroventricular delivery of recombinant human vascular endothelial growth factor in patients with amyotrophic lateral sclerosis. In this phase I study in patients with amyotrophic lateral sclerosis, the study drug was delivered using an implantable programmable pump connected to a catheter inserted in the frontal horn of the lateral cerebral ventricle. A first cohort received open label vascular endothelial growth factor (0.2, 0.8 and 2\u2009\u00b5g\/day), a second cohort received placebo, 0.8 or 2\u2009\u00b5g\/day of study dug. After the 3-month study period, all patients could participate in an open label extension study. In total, 18 patients with amyotrophic lateral sclerosis, seen at the University Hospitals in Leuven were included. The surgical procedure was well tolerated in most patients. One patient had transient postoperative seizures, due to an ischemic lesion along the catheter tract. The first 3-month study period was completed by 15\/18 patients. Administration of 2\u2009\u00b5g\/day vascular endothelial growth factor resulted in sustained detectable levels in cerebrospinal fluid. A pulmonary embolus occurred in 3 patients, in 1 patient in the first 3-month study, and in 2 patients during the open label extension study. The study drug was well tolerated in the other patients, for up to 6\u2009years in the open label extension study. Our study shows that intracerebroventricular administration of 2\u2009\u00b5g\/day of vascular endothelial growth factor to patients with amyotrophic lateral sclerosis is feasible, results in detectable cerebrospinal fluid levels and is well tolerated in most patients. The most common serious adverse event was a pulmonary embolus.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaa160","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T18:00:00Z","timestamp":1601402400000},"source":"Crossref","is-referenced-by-count":19,"title":["Intracerebroventricular delivery of vascular endothelial growth factor in patients with amyotrophic lateral sclerosis, a phase I study"],"prefix":"10.1093","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4010-2357","authenticated-orcid":false,"given":"Philip","family":"Van Damme","sequence":"first","affiliation":[{"name":"Department of Neurosciences, KU Leuven \u2013 University of Leuven, Leuven, Belgium"},{"name":"Laboratory of Neurobiology, VIB, Center for Brain & Disease Research, Leuven, Belgium"},{"name":"Department of Neurology, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Tilkin","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarina Jansson","family":"Mercer","sequence":"additional","affiliation":[{"name":"Newron Sweden AB"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1040-9411","authenticated-orcid":false,"given":"Joke","family":"Terryn","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann","family":"D\u2019Hondt","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Herne","sequence":"additional","affiliation":[{"name":"Newron Sweden AB"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Tousseyn","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospitals Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristl G","family":"Claeys","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospitals Leuven, Leuven, Belgium"},{"name":"Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, Experimental Neurology, KU Leuven \u2013 University of Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1036-1075","authenticated-orcid":false,"given":"Dietmar R","family":"Thal","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospitals Leuven, Belgium"},{"name":"Laboratory of Neuropathology, Department of Imaging and Pathology, KU Leuven \u2013 University of Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olof","family":"Zachrisson","sequence":"additional","affiliation":[{"name":"Newron Sweden AB"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per","family":"Almqvist","sequence":"additional","affiliation":[{"name":"Newron Sweden AB"},{"name":"Department of Clinical Neuroscience, Karolinska Instituted, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart","family":"Nuttin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Jerling","sequence":"additional","affiliation":[{"name":"Newron Sweden 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