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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, Woolley, Max, Brady, Alan, Williams, Julia, Johnson, David, Dailami, Narges, Gray, William ORCID:, Levo, Reeta, Saarma, Mart, Halldin, Christer, Marjamaa, Johan, Resendiz‐Nieves, Julio, Grubor, Irena, Lind, Göran, Eerola‐Rautio, Johanna, Mertsalmi, Tuomas, Andréasson, Mattias, Paul, Gesine, Rinne, Juha, Kivisaari, Riku, Bjartmarz, Hjalmar, Almqvist, Per, Varrone, Andrea, Scheperjans, Filip, Widner, Håkan and Svenningsson, Per 2023. Intraputamenal cerebral dopamine neurotrophic factor in Parkinson's disease: a randomized, double‐blind, multicenter phase 1 trial. Movement Disorders 38 (7) , pp. 1209-1222. 10.1002/mds.29426

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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 [18F]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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: License information from Publisher: LICENSE 1: URL:
Publisher: Wiley
ISSN: 0885-3185
Date of First Compliant Deposit: 23 May 2023
Date of Acceptance: 13 April 2023
Last Modified: 31 Aug 2023 20:17

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