Date: Tuesday, June 21, 2016
Session Title: Therapy in movement disorders: Gene and cell-based therapies
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: The objectives of this meta-analysis are: 1) to investigate the efficacy of AAV2-neurturin gene delivery for patients with Parkinson’s disease; 2) to compare AAV2-neurturin delivery in putamen only versus in putamen plus Substantia Nigra; and 3) to compare efficacy of gene delivery before 18 months and after 18 months of the injection.
Background: There is unmet need for developing better treatment strategies for Parkinson’s disease (PD). Gene delivery of neurturin, a natural analogue for glial derived neurotrophic factor, showed promising results in animal models and early open label trials. However, its efficacy has not been confirmed yet.
Methods: We searched PubMed for clinical trials (single arm and controlled trials) assessing the efficacy of AAV2-neurturin gene delivery in patients with PD. Data were extracted from eligible studies and were analyzed using RevMan and open meta[analyst] statistical packages. We conducted meta-regression to investigate whether the improvement in unified Parkinson’s disease rating scale (UPDRS III motor score) was associated with the target of gene delivery or follow up duration.
Results: Four studies (n=123 patients) were pooled in the final analysis. Compared with sham surgery, neurturin gene delivery was not significantly superior before 18 months but after 18-24 months (UPDRS III: MD -0.39, 95% CI [-4.15 to 3.36] vs. MD -4.49, 95% CI [-8.63 to -0.35], respectively; figure 1). Intraputamenal gene delivery was significantly better than gene delivery in putamen plus substantia nigra (UPDRS III: MD -12.76, 95% CI [-15.61 to -9.92] vs. MD -6.72, 95% CI [-10.38 to -3.06]; P=0.01; figure 2). Figure 1: Forest plot shows MD of change in UPDRS III from baseline to endpoints (neurturin vs. sham) with subgroup analysis according to follow up time. Figure 2: Forest plot shows MD of change in UPDRS III from baseline to endpoint (Putamen only vs. Putamen and Substantia Nigra).
|STUDY ID||Study designs||Target||End point*||Sample size||UPDRS III||HDAM**||PDQ-39***|
|Marks 2010||Randomized controlled trial||Putamen only||18||37/20||-11.96 (8.15)||-1.92 (3.18)||NR|
|Olanow 2015||Randomized controlled trial||Putamen and Substantia Nigra||24||23/25||-7 (9.92)||-1.9 (2.55)||-1.1 (10.39)|
|Raymond 2013||Open label single arm trial||Putamen and Substantia Nigra||24||6||-5.5 (10.68)||-2.3 (1.83)||0 (6.63)|
|Marks 2008||Open label single arm trial||Putamen only||12||12||-14 (8)||NR||NR|
Conclusions: Current evidence is insufficient to confirm the efficacy of AAV2-neurturin gene delivery. Our results suggest that the efficacy of AAV2-neurturin gene delivery in the putamen only should be evaluated by further randomized controlled trials with follow up duration beyond 18 months.
To cite this abstract in AMA style:A.G. Almraezy, H. Ahmed, M. Elnenny, A. Negida. Gene delivery of AAV2-neurturin for patients with Parkinson’s disease: A meta-analysis [abstract]. Mov Disord. 2016; 31 (suppl 2). http://www.mdsabstracts.org/abstract/gene-delivery-of-aav2-neurturin-for-patients-with-parkinsons-disease-a-meta-analysis/. Accessed February 18, 2018.
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MDS Abstracts - http://www.mdsabstracts.org/abstract/gene-delivery-of-aav2-neurturin-for-patients-with-parkinsons-disease-a-meta-analysis/