parkinsons-2019-keynote

Volume 3

Parkinson’s 2019

November 11-12, 2019

Page 13

Parkinson’s & Movement Disorders

November 11-12, 2019 | London, UK

International Conference on

Journal of Neurology and Clinical Neuroscience

J Neurol Clin Neurosci . | Volume 3

José Luis Lanciego Pérez

University of Navarra Medical School, Spain

Glucocerebrosidase Gene Therapy for Parkinson’s disease

utations in the GBA1 gene coding for the lysosomal enzyme glucocerebrosidase (GCase) are related to

increased incidence of synucleinopathies such as Parkinson’s disease (PD) and dementia with Lewy bodies

(DLB). Although the mechanisms through which GCase regulates the homeostasis of alpha-synuclein still are

not fully understood, the identification of reduced GCase lysosomal activity as a common feature sustaining

the neuropathological findings underlying PD and DLB -even when considering sporadic forms of these

synucleinopathies- has recently attracted strong interest in the field. Accordingly, a number of novel strategies

focused on increasing GCase activity to reduce alpha-synuclein burden and preventing dopaminergic neuronal

death have been designed. Here we have performed bilateral injections of a recombinant adeno-associated viral

vector serotype 9 coding for the mutated form of human alphasynuclein (rAAV9-SynA53T) for disease modelling

purposes, both in mice as well as in nonhuman primates (NHPs), further inducing a progressive neuronal death

in the substantia nigra pars compacta (SNc). Next, another rAAV9 coding for the GBA1 gene (rAAV9-GBA1)

was unilaterally delivered in the SNc of mice and NHPs one month after initial insult with rAAV9-SynA53T,

together with the contralateral delivery of an empty rAAV9 (rAAV9-null) for control purposes. Obtained

results showed that rAAV-mediated enhancement of GCase activity reduced alpha-synuclein burden, leading

to improved survival of dopaminergic neurons together with a reduction in microglial-driven pro-inflammatory

phenomena. Furthermore, the trans-synaptic “prionlike” spread of mutated alpha-synuclein was impeded upon

treatment with rAAV9-GBA1. Data reported here support the use of glucocerebrosidase gene therapy as a disease-

modifying treatment for PD and related synucleinopathies, also including sporadic forms of these disorders.

Biography

José Luis Lanciego Pérez is currently ahead of the Functional Neuroanatomy of Basal Ganglia Lab at the Center for Applied

Medical Research, University of Navarra. He has been working in the field of basal ganglia-related neurodegenerative disorders

for more than 20 years. He has published more than 100 papers in indexed journals, with an H index of 35 (May, 2019). In De-

cember 2006, his group received the credentials of “group of excellence” in the field of neurodegenerative disorders, issued by

the Spanish Ministry of Health. At present, his research group has a narrow focus on the implementation of a number of differ-

ent gene therapy strategies targeting neurodegenerative disorders caused by the pathological aggregation of misfolded proteins.