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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Gesine Paul-Visse
  • Olaf Zachrisson
  • Andrea Varrone
  • Per Almqvist
  • Markus Jerling
  • Goran Lind
  • Stig Rehncrona
  • Bengt Linderoth
  • Hjalmar Bjartmarz
  • Lisa L. Shafer
  • Robert Coffey
  • Mikael Svensson
  • Katarina Jansson Mercer
  • Anton Forsberg
  • Christer Halldin
  • Per Svenningsson
  • Hakan Widner
  • Jonas Frisen
  • Sven Palhagen
  • Anders Haegerstrand
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurologi
Originalspråkengelska
Sidor (från-till)1339-1346
TidskriftJournal of Clinical Investigation
Volym125
Utgivningsnummer3
StatusPublished - 2015
PublikationskategoriForskning
Peer review utfördJa

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