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Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson's disease patients

Paul-Visse, Gesine LU ; Zachrisson, Olaf; Varrone, Andrea; Almqvist, Per; Jerling, Markus; Lind, Goran; Rehncrona, Stig; Linderoth, Bengt; Bjartmarz, Hjalmar LU and Shafer, Lisa L., et al. (2015) In Journal of Clinical Investigation 125(3). p.1339-1346
Abstract
BACKGROUND. Recombinant human PDGF-BB (rhPDGF-BB) reduces Parkinsonian symptoms and increases dopamine transporter (DAT) binding in several animal models of Parkinson's disease (PD). Effects of rhPDGF-BB are the result of proliferation of ventricular wall progenitor cells and reversed by blocking mitosis. Based on these restorative effects, we assessed the safety and tolerability of intracerebroventricular (i.c.v.) rhPDGF-BB administration in individuals with PD. METHODS. We conducted a double-blind, randomized, placebo-controlled phase I/IIa study at two clinical centers in Sweden. Twelve patients with moderate PD received rhPDGF-BB via an implanted drug infusion pump and an investigational i.c.v. catheter. Patients were assigned to a... (More)
BACKGROUND. Recombinant human PDGF-BB (rhPDGF-BB) reduces Parkinsonian symptoms and increases dopamine transporter (DAT) binding in several animal models of Parkinson's disease (PD). Effects of rhPDGF-BB are the result of proliferation of ventricular wall progenitor cells and reversed by blocking mitosis. Based on these restorative effects, we assessed the safety and tolerability of intracerebroventricular (i.c.v.) rhPDGF-BB administration in individuals with PD. METHODS. We conducted a double-blind, randomized, placebo-controlled phase I/IIa study at two clinical centers in Sweden. Twelve patients with moderate PD received rhPDGF-BB via an implanted drug infusion pump and an investigational i.c.v. catheter. Patients were assigned to a dose cohort (0.2, 1.5, or 5 mu g rhPDGF-BB per day) and then randomized to active treatment or placebo (3:1) for a 12-day treatment period. The primary objective was to assess safety and tolerability of i.c.v.-delivered rhPDGF-BB. Secondary outcome assessments included several clinical rating scales and changes in DAT binding. The follow-up period was 85 days. RESULTS. All patients completed the study. There were no unresolved adverse events. Serious adverse events occurred in three patients; however, these were unrelated to rhPDGF-BB administration. Secondary outcome parameters did not show dose-dependent changes in clinical rating scales, but there was a positive effect on DAT binding in the right putamen. CONCLUSION. At all doses tested, i.c.v. administration of rhPDGF-BB was well tolerated. Results support further clinical development of rhPDGF-BB for patients with PD. (Less)
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Contribution to journal
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published
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in
Journal of Clinical Investigation
volume
125
issue
3
pages
1339 - 1346
publisher
The Journal of Clinical Investigation
external identifiers
  • wos:000350616500044
  • scopus:84924033997
ISSN
0021-9738
DOI
10.1172/JCI79635
language
English
LU publication?
yes
id
1277304e-b140-4db7-8aa3-ee7fed90ed1b (old id 5297192)
date added to LUP
2015-05-04 08:34:37
date last changed
2017-11-19 04:02:27
@article{1277304e-b140-4db7-8aa3-ee7fed90ed1b,
  abstract     = {BACKGROUND. Recombinant human PDGF-BB (rhPDGF-BB) reduces Parkinsonian symptoms and increases dopamine transporter (DAT) binding in several animal models of Parkinson's disease (PD). Effects of rhPDGF-BB are the result of proliferation of ventricular wall progenitor cells and reversed by blocking mitosis. Based on these restorative effects, we assessed the safety and tolerability of intracerebroventricular (i.c.v.) rhPDGF-BB administration in individuals with PD. METHODS. We conducted a double-blind, randomized, placebo-controlled phase I/IIa study at two clinical centers in Sweden. Twelve patients with moderate PD received rhPDGF-BB via an implanted drug infusion pump and an investigational i.c.v. catheter. Patients were assigned to a dose cohort (0.2, 1.5, or 5 mu g rhPDGF-BB per day) and then randomized to active treatment or placebo (3:1) for a 12-day treatment period. The primary objective was to assess safety and tolerability of i.c.v.-delivered rhPDGF-BB. Secondary outcome assessments included several clinical rating scales and changes in DAT binding. The follow-up period was 85 days. RESULTS. All patients completed the study. There were no unresolved adverse events. Serious adverse events occurred in three patients; however, these were unrelated to rhPDGF-BB administration. Secondary outcome parameters did not show dose-dependent changes in clinical rating scales, but there was a positive effect on DAT binding in the right putamen. CONCLUSION. At all doses tested, i.c.v. administration of rhPDGF-BB was well tolerated. Results support further clinical development of rhPDGF-BB for patients with PD.},
  author       = {Paul-Visse, Gesine and Zachrisson, Olaf and Varrone, Andrea and Almqvist, Per and Jerling, Markus and Lind, Goran and Rehncrona, Stig and Linderoth, Bengt and Bjartmarz, Hjalmar and Shafer, Lisa L. and Coffey, Robert and Svensson, Mikael and Mercer, Katarina Jansson and Forsberg, Anton and Halldin, Christer and Svenningsson, Per and Widner, Hakan and Frisen, Jonas and Palhagen, Sven and Haegerstrand, Anders},
  issn         = {0021-9738},
  language     = {eng},
  number       = {3},
  pages        = {1339--1346},
  publisher    = {The Journal of Clinical Investigation},
  series       = {Journal of Clinical Investigation},
  title        = {Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson's disease patients},
  url          = {http://dx.doi.org/10.1172/JCI79635},
  volume       = {125},
  year         = {2015},
}