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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 and Woolley, Max , et al. (2023) In Movement Disorders 38(7). p.1209-1222
Abstract

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.... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Parkinson Disease/drug therapy, Dopamine, Nerve Growth Factors/physiology, Dopaminergic Neurons, Drug Delivery Systems, Double-Blind Method
in
Movement Disorders
volume
38
issue
7
pages
1209 - 1222
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85159827480
  • pmid:37212361
ISSN
0885-3185
DOI
10.1002/mds.29426
language
English
LU publication?
yes
additional info
© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
id
4e72f6fa-3d86-4feb-9448-4d2684a7337f
date added to LUP
2024-10-28 14:02:25
date last changed
2025-07-09 01:57:10
@article{4e72f6fa-3d86-4feb-9448-4d2684a7337f,
  abstract     = {{<p>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).</p><p>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.</p><p>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.</p><p>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.</p><p>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.</p>}},
  author       = {{Huttunen, Henri J and Booms, Sigrid and Sjögren, Magnus and Kerstens, Vera and Johansson, Jarkko and Holmnäs, Rebecka and Koskinen, Jani and Kulesskaya, Natalia and Fazio, Patrik and Woolley, Max and Brady, Alan and Williams, Julia and Johnson, David and Dailami, Narges and Gray, William and Levo, Reeta and Saarma, Mart and Halldin, Christer and Marjamaa, Johan and Resendiz-Nieves, Julio and Grubor, Irena and Lind, Göran and Eerola-Rautio, Johanna and Mertsalmi, Tuomas and Andréasson, Mattias and Paul, Gesine and Rinne, Juha and Kivisaari, Riku and Bjartmarz, Hjálmar and Almqvist, Per and Varrone, Andrea and Scheperjans, Filip and Widner, Håkan and Svenningsson, Per}},
  issn         = {{0885-3185}},
  keywords     = {{Animals; Parkinson Disease/drug therapy; Dopamine; Nerve Growth Factors/physiology; Dopaminergic Neurons; Drug Delivery Systems; Double-Blind Method}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{1209--1222}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Movement Disorders}},
  title        = {{Intraputamenal Cerebral Dopamine Neurotrophic Factor in Parkinson's Disease : A Randomized, Double-Blind, Multicenter Phase 1 Trial}},
  url          = {{http://dx.doi.org/10.1002/mds.29426}},
  doi          = {{10.1002/mds.29426}},
  volume       = {{38}},
  year         = {{2023}},
}