Category: Parkinson’s Disease: Clinical Trials
Objective: To explore fluid-based biomarkers in subjects with advanced idiopathic Parkinson’s disease (PD) before and after intermittent intraputamenal monthly infusions of CDNF.
Background: CDNF is an unconventional neurotrophic factor shown to protect dopaminergic neurons and improve both motor and non-motor functions in rodent and primate models of PD via a unique multi-modal mechanism of action.
Method: A phase I-II clinical trial with 17 subjects with idiopathic PD of moderate severity were enrolled in a placebo-controlled, double-blind six-month main study followed by a six-month active treatment extension study. Patients were randomized in placebo (n=6) or incremental CDNF dosage (n=6 for low-mid dose and n=5 for low-mid-high dose) groups and received doses every four weeks via an intraputamenal drug delivery device (developed by co-sponsor Renishaw Plc). Primary endpoint was safety and tolerability. Serum samples were collected at baseline, and 8, 20, 24, 45 and 49 weeks after first dosing. Lumbar CSF samples were collected at baseline, and 20 and 45 weeks after first dosing. Serum and CSF samples were analyzed as exploratory endpoints for CDNF levels, anti-drug antibodies, α-synuclein (ELISA and RT-QuiC) and proteomic biomarkers (MRM-LC-MS/MS assay). Patients were genetically profiled by next-generation sequencing of saliva samples.
Results: The full results will be available after the completion of the six-month active treatment extension study in August 2020. Total, Ser129-phosphorylated and oligomeric α-synuclein were determined from serum and CSF by ELISA. CSF samples were analyzed for α-synuclein seeding activity by RT-QuiC. In the CSF proteomics study, biomarker profiles of the study subjects were compared to CSF samples from healthy age-matched controls in a discovery screen. Subsequently, selected biomarkers from the screen were monitored as potential signs of treatment response on a targeted proteomics assay and compared between the dosing groups.
Conclusion: The results from these serum and CSF analyses are expected to provide further insight into the biological responses to intraputamenal CDNF infusions in advanced PD patients.
To cite this abstract in AMA style:
H. Huttunen, S. Booms, H. Abdesselem, N. Majbour, O. El-Agnaf, I. Poggiolini, L. Parkkinen, A. Cryar, E. Sirka, J. Harris, M. Dove, M. Sjögren, M. Woolley, B. Murphy, P. Fielder, J. Baker, P. Skinner, M. Andreasson, G. Paul-Visse, R. Kivisaari, H. Bjartmarz, P. Almqvist, P. Almqvist, G. Lind, F. Scheperjans, H. Widner, P. Svenningsson. Phase I-II first-in-human clinical trial of intraputamenal CDNF in Parkinson’s disease: Exploratory fluid-based biomarker endpoints of the 12-month treatment period [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/phase-i-ii-first-in-human-clinical-trial-of-intraputamenal-cdnf-in-parkinsons-disease-exploratory-fluid-based-biomarker-endpoints-of-the-12-month-treatment-period/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/phase-i-ii-first-in-human-clinical-trial-of-intraputamenal-cdnf-in-parkinsons-disease-exploratory-fluid-based-biomarker-endpoints-of-the-12-month-treatment-period/