Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial

  title={Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial},
  author={William J Marks and Raymond T. Bartus and Jo{\~a}o Siffert and Charles S. Davis and Andres Lozano and Nicholas M. Boulis and Jerrold L. Vitek and Mark Stacy and Dennis A Turner and Leo Verhagen and Roy A. E. Bakay and Ray L. Watts and Barton L. Guthrie and Joseph Jankovic and Richard K. Jr. Simpson and Michele Tagliati and Ron L Alterman and Matthew B. Stern and Gordon Baltuch and Philip A. Starr and Paul S. Larson and Jill L Ostrem and John D. Nutt and Karl D. Kieburtz and Jeffrey H. Kordower and C. Warren Olanow},
  journal={The Lancet Neurology},

[Gene therapy for Parkinson's disease].

  • S. Muramatsu
  • Biology
    Rinsho shinkeigaku = Clinical neurology
  • 2012
The efficacy outcomes are encouraging and indicate that the AAV vector-mediated gene transfer of AADC may benefit advanced PD patients, and a similar approach, delivering A AV vector carrying A ADC gene into the putamen ameliorated the symptoms in children with AADc deficiency.

Safety/feasibility of targeting the substantia nigra with AAV2-neurturin in Parkinson patients

Bilateral stereotactic administration of CERE-120 to the SN plus putamen in PD is feasible and this evaluation provides initial empirical support that it is safe and well-tolerated, according to two-year safety data.

AAV2-neurturin (CERE-120) for Parkinson's disease

This review discusses early experiences with glial-derived neurotrophic factor in PD, the initial studies using AAV2-neurturin in PD patients, the lessons learned from these studies and the future directions of this therapy.

Gene delivery of neurturin to putamen and substantia nigra in Parkinson disease: A double‐blind, randomized, controlled trial

A 12‐month double‐blind sham‐surgery–controlled trial assessing adeno‐associated virus type 2 (AAV2)‐neurturin injected into the putamen bilaterally failed to meet its primary endpoint, but showed

Open‐label surgical trials for Parkinson disease: Time for reconsideration

Six consecutive times in the past decade, a surgically administered experimental therapy for Parkinson disease (PD) that had shown great promise in the laboratory and positive results in open-label

The Placebo Response in Double-Blind Randomised Trials Evaluating Regenerative Therapies for Parkinson's Disease: A Systematic Review and Meta-Analysis.

The analysis of the evidence generated by the completed and published trials indicates that placebo controlled trials are not necessary to advance and evaluate the safety and efficacy of emerging regenerative therapies for PD.

Data-driven evolution of neurosurgical gene therapy delivery in Parkinson’s disease

The challenges with surgical delivery of gene therapy vectors that limited therapeutic outcomes in these trials are reviewed, particularly the lack of real-time monitoring of vector administration.



Striatal delivery of neurturin by CERE-120, an AAV2 vector for the treatment of dopaminergic neuron degeneration in Parkinson's disease.

It is found that the kinetics and pattern of NTN expression in the rat striatum following injection of CERE-120 is rapid, increases significantly up to 4 weeks, and exhibits a stable volume of distribution thereafter for at least 1 year, the longest time-point evaluated.

Transgene expression, bioactivity, and safety of CERE-120 (AAV2-neurturin) following delivery to the monkey striatum.

Estimation of the expression, bioactivity and safety of CERE-120, an adeno-associated virus type-2 (AAV2) vector encoding NTN, following delivery to the striatum of nonhuman primates provide substantial novel evidence for the potential utility of Cere-120 as a novel treatment for PD and support ongoing clinical trials testing CUE-120 in PD patients.

Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD

GDNF administered by ICV injection is biologically active as evidenced by the spectrum of AE encountered in this study, and did not improve parkinsonism, possibly because GDNF did not reach the target tissues—putamen and substantia nigra.

Bioactivity of AAV2‐neurturin gene therapy (CERE‐120): Differences between Parkinson's disease and nonhuman primate brains

These data provide the first evidence that gene therapy can increase expression of a neurotrophic‐factor deep in the PD brain and that clear but modest enhancement of degenerating neurons can be induced, suggesting that serious axon‐transport deficits reduced the bioactivity of AAV2‐NRTN by limiting the protein exposed to the cell body.

Transplantation of embryonic dopamine neurons for severe Parkinson's disease.

After improvement in the first year, dystonia and dyskinesias recurred in 15 percent of the patients who received transplants, even after reduction or discontinuation of the dose of levodopa.

Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor.

Analysis of the data in this open-label study demonstrates the safety and potential efficacy of unilateral intraputaminal GDNF infusion in 10 patients with advanced Parkinson disease.

Striatal delivery of CERE‐120, an AAV2 vector encoding human neurturin, enhances activity of the dopaminergic nigrostriatal system in aged monkeys

Results are consistent with the neurotrophic effects of NTN on the dopaminergic nigrostriatal system and extend the growing body of evidence supporting the concept that AAV2‐NTN may have therapeutic benefit for Parkinson's disease.

A double‐blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease

Fetal nigral transplantation currently cannot be recommended as a therapy for PD based on results, and Stratification based on disease severity showed a treatment effect in milder patients.