Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2–neurturin) to patients with idiopathic Parkinson's disease: an open-label, phase I trial

SummaryBackgroundThere is an urgent need for therapies that slow or reverse the progression of Parkinson's disease (PD). Neurotrophic factors can improve the function of degenerating neurons and protect against further neurodegeneration, and gene transfer might be a means to deliver effectively these factors to the brain. The aim of this study was to assess the safety, tolerability, and potential efficacy of gene delivery of the neurotrophic factor neurturin.MethodsIn this phase I, open-label clinical trial, 12 patients aged 35–75 years with a diagnosis of PD for at least 5 years in accordance with the UK Brain Bank Criteria received bilateral, stereotactic, intraputaminal injections of adeno-associated virus serotype 2–neurturin (CERE-120). The first six patients received doses of 1·3×1011 vector genomes (vg)/patient, and the next six patients received 5·4×1011 vg/patient. This trial is registered with ClinicalTrials.gov, number NCT00252850.FindingsThe procedure was well tolerated. Extensive safety monitoring in all patients revealed no clinically significant adverse events at 1 year. Several secondary measures of motor function showed improvement at 1 year; for example, a mean improvement in the off-medication motor subscore of the Unified Parkinson's Disease Rating Scale (UPDRS) of 14 points (SD 8; p=0.000121 [36% mean increase; p=0.000123]) and a mean increase of 2·3 h (2; 25% group mean increase; p=0·0250) in on time without troublesome dyskinesia were seen. Improvements in several secondary measures were not significant, including the timed walking test in the off condition (p=0·053), the Purdue pegboard test of hand dexterity (p=0·318), the reduction in off time (p=0·105), and the activities of daily living subscore (part II) of the UPDRS (p=0·080). 18F-levodopa-uptake PET did not change after treatment with either dose of CERE-120.InterpretationThe initial data support the safety, tolerability, and potential efficacy of CERE-120 as a possible treatment for PD; however, these results must be viewed as preliminary until data from blinded, controlled clinical trials are available.FundingCeregene; Michael J Fox Foundation for Parkinson's Research.