Category: Parkinson’s Disease: Clinical Trials
Objective: In the first-in-man clinical study of intermittent intraputamenal monthly infusions of CDNF in subjects with moderately advanced PD, we explored cerebrospinal fluid (CSF) biomarkers before, during and after the treatment using proteomics.
Background: Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that protects dopamine neurons via a unique multi-modal mechanism of action.
Method: A randomized phase I-II trial in 17 patients with moderate PD was conducted with placebo or incremental CDNF dosing for 6 months followed by a six-month active treatment extension study. A bone-anchored CED device (Renishaw Neuro Solutions Ltd) was used for intraputamenal infusion. Lumbar CSF samples were collected at baseline and at 6 and 12 months. In a discovery proteomics study, baseline CSF samples (n=14) were compared to healthy age-matched controls (n=15). Based on this data, a 50-protein panel was selected for a targeted proteomics study in which samples from baseline and after 6 and 12 months of treatment were quantitatively compared using triple quadrupole LC-MS/MS system, operated in timed multiple reaction monitoring mode (MRM). The levels of total and oligomeric α-synuclein in CSF from the same timepoints were determined by ELISA. All subjects were genotyped (a panel of 23 PD-related genes).
Results: Data from the targeted proteomics study suggested that 5 of 14 (36%) subjects receiving CDNF showed a consorted change in the CSF biomarker profile. One of the patients, a heterozygote for LRRK2(G2019S), initially during placebo exposure did not show significant changes in the CSF profile but after switching to CDNF showed a clear change. Bioinformatic analysis suggested that 12 of the 21 CSF markers that showed a consorted change in CSF biomarker profile in the responding patients were associated either with lysosomal function and autophagy (6) or immune response (6), linking the response to the proteostatic mechanisms of action of CDNF.
Conclusion: While this first-in-human clinical study was not powered to assess efficacy, a subset of patients showed potential signs of biological response to CDNF treatment. CSF biomarker profiling identified a set of proteins changing in concert in a subgroup of subjects. The results suggest that patients with LRRK2(G2019S) mutation could present a target subtype of PD for next clinical studies with CDNF.
To cite this abstract in AMA style:
H. Huttunen, S. Booms, M. Sjögren, A. Cryar, J. Harris, E. Sirka, M. Dove, N. Majbour, H. Abdesselem, O. El-Agnaf, J. Koskinen, R. Holmnäs, V. Kerstens, J. Johansson, J. Rinne, A. Varrone, M. Woolley, B. Murphy, P. Fielder, J. Baker, P. Skinner, M. Andreasson, G. Paul-Visse, R. Kivisaari, H. Bjartmarz, G. Lind, P. Almqvist, F. Scheperjans, H. Widner, P. Svenningsson. FIRST-IN-MAN CLINICAL TRIAL OF INTRAPUTAMENAL CDNF IN PARKINSON’S DISEASE FINDS A CONSORTED BIOMARKER RESPONSE IN A SUBGROUP OF SUBJECTS [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/first-in-man-clinical-trial-of-intraputamenal-cdnf-in-parkinsons-disease-finds-a-consorted-biomarker-response-in-a-subgroup-of-subjects/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/first-in-man-clinical-trial-of-intraputamenal-cdnf-in-parkinsons-disease-finds-a-consorted-biomarker-response-in-a-subgroup-of-subjects/