Data-driven evolution of neurosurgical gene therapy delivery in Parkinson's disease.
J Neurol Neurosurg Psychiatry
; 91(11): 1210-1218, 2020 11.
Article
en En
| MEDLINE
| ID: mdl-32732384
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
/
Sustancia Negra
/
Imagen por Resonancia Magnética
/
Terapia Genética
/
Procedimientos Neuroquirúrgicos
/
Cuerpo Estriado
/
Vectores Genéticos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Neurol Neurosurg Psychiatry
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos