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Intracerebroventricular delivery of vascular endothelial growth factor in patients with amyotrophic lateral sclerosis, a phase I study

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 d...

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Autores principales: Van Damme, Philip, Tilkin, Petra, Mercer, Katarina Jansson, Terryn, Joke, D’Hondt, Ann, Herne, Nina, Tousseyn, Thomas, Claeys, Kristl G, Thal, Dietmar R, Zachrisson, Olof, Almqvist, Per, Nuttin, Bart, Jerling, Markus, Bernadotte, Folke, Haegerstrand, Anders, Robberecht, Wim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099230/
https://www.ncbi.nlm.nih.gov/pubmed/33977260
http://dx.doi.org/10.1093/braincomms/fcaa160
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author Van Damme, Philip
Tilkin, Petra
Mercer, Katarina Jansson
Terryn, Joke
D’Hondt, Ann
Herne, Nina
Tousseyn, Thomas
Claeys, Kristl G
Thal, Dietmar R
Zachrisson, Olof
Almqvist, Per
Nuttin, Bart
Jerling, Markus
Bernadotte, Folke
Haegerstrand, Anders
Robberecht, Wim
author_facet Van Damme, Philip
Tilkin, Petra
Mercer, Katarina Jansson
Terryn, Joke
D’Hondt, Ann
Herne, Nina
Tousseyn, Thomas
Claeys, Kristl G
Thal, Dietmar R
Zachrisson, Olof
Almqvist, Per
Nuttin, Bart
Jerling, Markus
Bernadotte, Folke
Haegerstrand, Anders
Robberecht, Wim
author_sort Van Damme, Philip
collection PubMed
description 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 µg/day), a second cohort received placebo, 0.8 or 2 µg/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 µg/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 years in the open label extension study. Our study shows that intracerebroventricular administration of 2 µg/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.
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spelling pubmed-80992302021-05-10 Intracerebroventricular delivery of vascular endothelial growth factor in patients with amyotrophic lateral sclerosis, a phase I study Van Damme, Philip Tilkin, Petra Mercer, Katarina Jansson Terryn, Joke D’Hondt, Ann Herne, Nina Tousseyn, Thomas Claeys, Kristl G Thal, Dietmar R Zachrisson, Olof Almqvist, Per Nuttin, Bart Jerling, Markus Bernadotte, Folke Haegerstrand, Anders Robberecht, Wim Brain Commun Original Article 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 µg/day), a second cohort received placebo, 0.8 or 2 µg/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 µg/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 years in the open label extension study. Our study shows that intracerebroventricular administration of 2 µg/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. Oxford University Press 2020-09-29 /pmc/articles/PMC8099230/ /pubmed/33977260 http://dx.doi.org/10.1093/braincomms/fcaa160 Text en © The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Article
Van Damme, Philip
Tilkin, Petra
Mercer, Katarina Jansson
Terryn, Joke
D’Hondt, Ann
Herne, Nina
Tousseyn, Thomas
Claeys, Kristl G
Thal, Dietmar R
Zachrisson, Olof
Almqvist, Per
Nuttin, Bart
Jerling, Markus
Bernadotte, Folke
Haegerstrand, Anders
Robberecht, Wim
Intracerebroventricular delivery of vascular endothelial growth factor in patients with amyotrophic lateral sclerosis, a phase I study
title Intracerebroventricular delivery of vascular endothelial growth factor in patients with amyotrophic lateral sclerosis, a phase I study
title_full Intracerebroventricular delivery of vascular endothelial growth factor in patients with amyotrophic lateral sclerosis, a phase I study
title_fullStr Intracerebroventricular delivery of vascular endothelial growth factor in patients with amyotrophic lateral sclerosis, a phase I study
title_full_unstemmed Intracerebroventricular delivery of vascular endothelial growth factor in patients with amyotrophic lateral sclerosis, a phase I study
title_short Intracerebroventricular delivery of vascular endothelial growth factor in patients with amyotrophic lateral sclerosis, a phase I study
title_sort intracerebroventricular delivery of vascular endothelial growth factor in patients with amyotrophic lateral sclerosis, a phase i study
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099230/
https://www.ncbi.nlm.nih.gov/pubmed/33977260
http://dx.doi.org/10.1093/braincomms/fcaa160
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