Intraputamenal Cerebral Dopamine Neurotrophic Factor in Parkinson's Disease: A Randomized, Double-Blind, Multicenter Phase 1 Trial
: Huttunen Henri J, Booms Sigrid, Sjögren Magnus, Kerstens Vera, Johansson Jarkko, Holmnäs Rebecka, Koskinen Jani, Kulesskaya Natalia, Fazio Patrik, Woolley Max, Brady Alan, Williams Julia, Johnson David, Dailami Narges, Gray William, Levo Reeta, Saarma Mart, Halldin Christer, Marjamaa Johan, Resendiz-Nieves Julio, Grubor Irena, Lind Göran, Eerola-Rautio Johanna, Mertsalmi Tuomas, Andreasson Mattias, Paul Gesine, Rinne Juha, Kivisaari Riku, Bjartmarz Hjalmar, Almqvist Per, Varrone Andrea, Scheperjans Filip, Widner Håkan, Svenningsson Per
Publisher: Wiley
: 2023
: Movement Disorders
: MOVEMENT DISORDERS
: MOVEMENT DISORD
: 38
: 7
: 1209
: 1222
: 15
: 0885-3185
: 1531-8257
DOI: https://doi.org/10.1002/mds.29426
: https://doi.org/10.1002/mds.29426
: https://research.utu.fi/converis/portal/detail/Publication/179763236
Background: Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that protects dopamine neurons and improves motor function in animal models of Parkinson's disease (PD).
Objective: The primary objectives of this study were to assess the safety and tolerability of both CDNF and the drug delivery system (DDS) in patients with PD of moderate severity.
Methods: We assessed the safety and tolerability of monthly intraputamenal CDNF infusions in patients with PD using an investigational DDS, a bone-anchored transcutaneous port connected to four catheters. This phase 1 trial was divided into a placebo-controlled, double-blind, 6-month main study followed by an active-treatment 6-month extension. Eligible patients, aged 35 to 75 years, had moderate idiopathic PD for 5 to 15 years and Hoehn and Yahr score ≤ 3 (off state). Seventeen patients were randomized to placebo (n = 6), 0.4 mg CDNF (n = 6), or 1.2 mg CDNF (n = 5). The primary endpoints were safety and tolerability of CDNF and DDS and catheter implantation accuracy. Secondary endpoints were measures of PD symptoms, including Unified Parkinson's Disease Rating Scale, and DDS patency and port stability. Exploratory endpoints included motor symptom assessment (PKG, Global Kinetics Pty Ltd, Melbourne, Australia) and positron emission tomography using dopamine transporter radioligand [18 F]FE-PE2I.
Results: Drug-related adverse events were mild to moderate with no difference between placebo and treatment groups. No severe adverse events were associated with the drug, and device delivery accuracy met specification. The severe adverse events recorded were associated with the infusion procedure and did not reoccur after procedural modification. There were no significant changes between placebo and CDNF treatment groups in secondary endpoints between baseline and the end of the main and extension studies.
Conclusions: Intraputamenally administered CDNF was safe and well tolerated, and possible signs of biological response to the drug were observed in individual patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
