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

Autor:	Richardson RM; Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts, USA mark.richardson@mgh.harvard.edu.; Harvard Medical School, Boston, Massachusetts, USA., Bankiewicz KS; Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.; Department of Neurological Surgery, Ohio State University College of Medicine, Columbus, Ohio, USA., Christine CW; Department of Neurology, University of California San Francisco, San Francisco, California, USA., Van Laar AD; Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.; Brain Neurotherapy Bio, Inc, Columbus, Ohio, USA., Gross RE; Department of Neurosurgery, Emory University, Atlanta, Georgia, USA.; Department of Neurology, Emory University, Atlanta, Georgia, USA., Lonser R; Department of Neurological Surgery, Ohio State University College of Medicine, Columbus, Ohio, USA., Factor SA; Department of Neurology, Emory University, Atlanta, Georgia, USA., Kostyk SK; Departments of Neuroscience and Neurology, Ohio State University College of Medicine, Columbus, Ohio, USA., Kells AP; Brain Neurotherapy Bio, Inc, Columbus, Ohio, USA., Ravina B; Praxis Precision Medicines, Inc, Cambridge, Massachusetts, USA., Larson PS; Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Jazyk:	angličtina
Zdroj:	Journal of neurology, neurosurgery, and psychiatry [J Neurol Neurosurg Psychiatry] 2020 Nov; Vol. 91 (11), pp. 1210-1218. Date of Electronic Publication: 2020 Jul 30.
DOI:	10.1136/jnnp-2020-322904
Abstrakt:	Loss of nigrostriatal dopaminergic projection neurons is a key pathology in Parkinson's disease, leading to abnormal function of basal ganglia motor circuits and the accompanying characteristic motor features. A number of intraparenchymally delivered gene therapies designed to modify underlying disease and/or improve clinical symptoms have shown promise in preclinical studies and subsequently were evaluated in clinical trials. Here we review the challenges with surgical delivery of gene therapy vectors that limited therapeutic outcomes in these trials, particularly the lack of real-time monitoring of vector administration. These challenges have recently been addressed during the evolution of novel techniques for vector delivery that include the use of intraoperative MRI. The preclinical development of these techniques are described in relation to recent clinical translation in an adeno-associated virus serotype 2-mediated human aromatic L-amino acid decarboxylase gene therapy development programme. This new paradigm allows visualisation of the accuracy and adequacy of viral vector delivery within target structures, enabling intertrial modifications in surgical approaches, cannula design, vector volumes and dosing. The rapid, data-driven evolution of these procedures is unique and has led to improved vector delivery. Competing Interests: Competing interests: RMR, CWC, ADVL, REG and SAF received grants from Voyager Therapeutics, Inc. KSB received grants and personal fees from Voyager Therapeutics. Voyager Therapeutics is funding this research and is developing products related to the research described in this paper. REG serves as a consultant to Voyager Therapeutics and personally receives compensation for these services. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict-of-interest policies. RL received consulting fees from Voyager Therapeutics. SKK has nothing to disclose. APK is a former employee of Voyager Therapeutics and owns stock in that company. BR is a former employee of Voyager Therapeutics. PSL has received grants from Voyager Therapeutics and non-financial support from ClearPoint Neuro (formerly MRI Interventions, Inc). (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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