Phase I Study of CERE-120 [Adeno-Associated Virus (AAV)-Neuturin (NTN)] to Assess the Safety and Tolerability of Intraputaminal Delivery

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 slow the disease course in PD. Continuous and targeted administration of NTN to nigrostriatal neurons can be achieved using gene transfer (gene therapy) via an adeno-associated virus (AAV)-based gene transfer vector (CERE-120).

Project Description:
This Phase I clinical trial investigated the safety of CERE-120 when surgically delivered to the striatum of subjects with PD. The study included 12 subjects with advanced PD; subjects received either low-dose or high-dose CERE-120. Safety was assessed by evaluating spontaneously reported adverse events, clinical laboratory test results, imaging (MRI), neuropsychometric tests, and periodic clinical evaluations In addition, whether CERE-120 improves the function of the nigrostriatal system, resulting in Symptoms & Side Effects benefit to patients was also assessed by examining several efficacy measures at periodic clinical evaluations. These included the UPDRS motor scale while the subject had been off standard antiparkinsonian medications, timed motor tasks, patient diaries, and clinical global impression ratings. Neuroimaging using 18F-dopa PET scans was also performed.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This clinical trial protocol tested whether gene delivery of the growth factor neurturin via CERE-120 might be safe and well tolerated in Parkinson’s disease patients. Preliminary assessments of the efficacy of CERE-120 were also examined. 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:
A favorable safety outcome in this Phase I clinical trial led to the planning and execution of a larger, sham-surgery controlled, double-blinded Phase II clinical trial to generate meaningful data regarding the potential of CERE-120 to treat PD. This study is ongoing.