Objective/Rationale:
Neurotrophic factors including neurturin (NTN) have been shown to effectively augment the function and prevent the death of dopaminergic nigrostriatal neurons in animal models of Parkinsons’s disease (PD). Thus, NTN administration may potentially provide Symptoms & Side Effects benefit as well as modify the disease course in PD. CERE-120, a gene transfer vector to deliver NTN to the striatum, has been demonstrated to be safe and well tolerated in a Phase I clinical trial in subjects with advanced PD.
Project Description:
A Phase II clinical trial is now proposed to evaluate whether CERE-120 provides clinical benefit in subjects with advanced PD. A larger number of subjects will be studied (51 subjects total), CERE-120 will be compared to a control (sham surgery) group, and a randomized, double-blind design will be utilized. The primary outcome to be compared between the two groups is motor function (UPDRS motor) at 12 months after surgery, assessed at a time when dopaminergic medication has worn off. Other measures include dyskinesia ratings, timed motor tasks, patient diaries, and clinical global impression ratings. Safety measures will be carefully monitored throughout the study. Additionally, neuroimaging using 18F-dopa PET scans will be performed in a subset of the subjects.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This is a double-blind, sham surgery-controlled clinical trial proposal to determine whether gene delivery of the growth factor NTN via CERE-120 provides clinical benefit in Parkinson’s disease patients. Unlike current therapies for PD, growth factor gene delivery offers the potential to prevent cell loss and stimulate cell function, thus modifying disease progression and symptoms.
Anticipated Outcome:
The goal of this work is to generate sufficiently rigorous efficacy and safety data with a sham surgery-controlled, double-blind design to enable investigators to ascertain the effectiveness and safety of CERE-120. Pending a favorable efficacy and safety outcome in this clinical trial, further clinical testing would be initiated.