Intraputamenal Cerebral Dopamine Neurotrophic Factor in Parkinson's Disease: A Randomized, Double-Blind, Multicenter Phase 1 Trial.

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.

Transcutaneous port for levodopa/carbidopa intestinal gel administration in Parkinson's disease.

OBJECTIVE: To evaluate the safety and tolerability of the T-Port(®) for intestinal infusion of levodopa/carbidopa gel in patients with advanced Parkinson's disease (PD). METHODS: This prospective study was carried out in 24 patients with PD (15 males, mean age 61.8 years, mean duration PD 18.7 years). All adverse device effects were evaluated at 2 weeks, 3 months and 6 months and until explantation or death. RESULTS: Post-operative complications were similar to endoscopic gastrojejunostomy placement (four peritoneal irritation, one pocket pain). Eight patients with prior experience with the endoscopic gastrojejunostomy preferred the T-Port. The total device experience was 83.6 years, and the average survival time was 3.6 (range 1.1-5.2) years. Six T-Ports were still in use, and two patients had died due to non-device-related reasons. Sixteen T-Ports had been explanted due to 15 stoma reactions (14 inflammations and one infection) and one tilting of the T-Port. The T-Ports were replaced with endoscopic gastrojejunostomy system as replacements with T-Ports were not part of the study. Only two device malfunctions occurred (one catheter breakage at 3 year post-implant and one T-Port leakage of levodopa/carbidopa gel). No tube kinking, dislocation or blockage occurred. The number of adverse device effects proved to be significantly lower as compared to the endoscopic gastrojejunostomy literature data. CONCLUSIONS: The T-Port is safe and well tolerated, and the low number of tube problems is a potential advantage compared with the endoscopic gastrojejunostomy system. Proper cleaning and local treatment of the stoma site around the T-Port are essential to prolong its longevity.