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

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 dise...

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Autores principales: Richardson, R Mark, Bankiewicz, Krystof S, Christine, Chadwick W, Van Laar, Amber D, Gross, Robert E, Lonser, Russell, Factor, Stewart A, Kostyk, Sandra K, Kells, Adrian P, Ravina, Bernard, Larson, Paul S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569395/
https://www.ncbi.nlm.nih.gov/pubmed/32732384
http://dx.doi.org/10.1136/jnnp-2020-322904
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author Richardson, R Mark
Bankiewicz, Krystof S
Christine, Chadwick W
Van Laar, Amber D
Gross, Robert E
Lonser, Russell
Factor, Stewart A
Kostyk, Sandra K
Kells, Adrian P
Ravina, Bernard
Larson, Paul S
author_facet Richardson, R Mark
Bankiewicz, Krystof S
Christine, Chadwick W
Van Laar, Amber D
Gross, Robert E
Lonser, Russell
Factor, Stewart A
Kostyk, Sandra K
Kells, Adrian P
Ravina, Bernard
Larson, Paul S
author_sort Richardson, R Mark
collection PubMed
description 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.
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spelling pubmed-75693952020-10-20 Data-driven evolution of neurosurgical gene therapy delivery in Parkinson’s disease Richardson, R Mark Bankiewicz, Krystof S Christine, Chadwick W Van Laar, Amber D Gross, Robert E Lonser, Russell Factor, Stewart A Kostyk, Sandra K Kells, Adrian P Ravina, Bernard Larson, Paul S J Neurol Neurosurg Psychiatry Neurosurgery 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. BMJ Publishing Group 2020-11 2020-07-30 /pmc/articles/PMC7569395/ /pubmed/32732384 http://dx.doi.org/10.1136/jnnp-2020-322904 Text en © 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. http://creativecommons.org/licenses/by-nc/4.0/ http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Neurosurgery
Richardson, R Mark
Bankiewicz, Krystof S
Christine, Chadwick W
Van Laar, Amber D
Gross, Robert E
Lonser, Russell
Factor, Stewart A
Kostyk, Sandra K
Kells, Adrian P
Ravina, Bernard
Larson, Paul S
Data-driven evolution of neurosurgical gene therapy delivery in Parkinson’s disease
title Data-driven evolution of neurosurgical gene therapy delivery in Parkinson’s disease
title_full Data-driven evolution of neurosurgical gene therapy delivery in Parkinson’s disease
title_fullStr Data-driven evolution of neurosurgical gene therapy delivery in Parkinson’s disease
title_full_unstemmed Data-driven evolution of neurosurgical gene therapy delivery in Parkinson’s disease
title_short Data-driven evolution of neurosurgical gene therapy delivery in Parkinson’s disease
title_sort data-driven evolution of neurosurgical gene therapy delivery in parkinson’s disease
topic Neurosurgery
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569395/
https://www.ncbi.nlm.nih.gov/pubmed/32732384
http://dx.doi.org/10.1136/jnnp-2020-322904
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