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Volume 3 Current Research: Integrative Medicine Nursing Care & ICNND 2018
October 22-23, 2018
October 22-23, 2018 Madrid, Spain
46th World Congress on
Nursing Care, Neurology and Neuromuscular Diseases
Real-timeMRI-guided delivery ofAAV2-AADC gene therapy for parkinson’s disease andAADCdeficiency
in children
Krzysztof S Bankiewicz
University of California, USA
Gene transfer technology can correct genetic mutations in the brain. Neuro gene delivery via direct intrapranchymal injections
of Adeno-Associated Viral (AAV) vectors is a locally administered treatment that requires accurate delivery to maximize
safety and efficacy. Gene therapy using Adeno-Associated Virus (AAV2) carrying the Amino Acid Decarboxylase (AADC) gene
has the potential to improve the clinical response to levodopa when infused into the putamen of Parkinson’s Disease patients (PD)
or to generate dopamine production in children with AADC gene mutation after direct administration to substantia nigra and
ventral tegmental area. Prior clinical trials have shown possible benefit but may have been limited by inadequate anatomical vector
delivery or off-target vector distribution. Using intraoperative MRI and co-infusing the vector with gadoteridol now allows real-time
visualization of infusions. Analysis of bilateral MRI-guided putaminal infusions for 15 Parkinsonian patients and 3 children with
AADC deficiency in an ongoing Phase Ib/2 AAV2-AADC clinical trial was performed. T1-weighed images were used to calculate
coverage of the putamen. The infusion strategy evolved during the trial to maximize coverage of the putamen by modifying the
cannula design, increasing the infusion volumes and altering the cannula trajectories. Real-time MRI-guided delivery allows various
infusion strategies to be employed to maximize target coverage. MR-guided infusions of the vector into the midbrain of AADC-
deficient children resulted in 100% coverage of target structures. In both PD and AADC deficient children AAV-AADC gene transfer
was able to significantly increase clinical outcome as manifested by 4 hours increase in ON time in PD patients at 12 months and
increase of motor performance in AADC-deficient children. In addition, significant reduction of oculomotor crises was observed
as well. These results show that advances in surgical techniques have markedly improved vector delivery and that AAV2-AADC has
strong therapeutic potential in both indications presented here.
J Current Res: Int Medicine 2018, Volume 3
DOI: 10.4172/2529-797X-C2-006