Highlights
- •Convection-enhanced delivery of MANF in porcine putamen and substantia nigra results in widespread distribution.
- •MANF distribution correlates well with co-infused gadolinium-DTPA visualised with real-time MRI.
- •This study confirms the translational potential of CED of MANF as a novel treatment strategy for Parkinson's Disease.
Abstract
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a 20 kDa human protein which has both neuroprotective and neurorestorative activity on
dopaminergic neurons and therefore may have application for the treatment of Parkinson's
Disease. The aims of this study were to determine the translational potential of convection-enhanced
delivery (CED) of MANF for the treatment of PD by studying its distribution in porcine
putamen and substantia nigra and to correlate histological distribution with co-infused
gadolinium-DTPA using real-time magnetic resonance imaging. We describe the distribution
of MANF in porcine putamen and substantia nigra using an implantable CED catheter
system using co-infused gadolinium-DTPA to allow real-time MRI tracking of infusate
distribution. The distribution of gadolinium-DTPA on MRI correlated well with immunohistochemical
analysis of MANF distribution. Volumetric analysis of MANF IHC staining indicated
a volume of infusion (Vi) to volume of distribution (Vd) ratio of 3 in putamen and
2 in substantia nigra.
This study confirms the translational potential of CED of MANF as a novel treatment
strategy in PD and also supports the co-infusion of gadolinium as a proxy measure
of MANF distribution in future clinical studies. Further study is required to determine
the optimum infusion regime, flow rate and frequency of infusions in human trials.
Keywords
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Article info
Publication history
Published online: August 05, 2015
Accepted:
August 3,
2015
Received:
June 17,
2015
Identification
Copyright
© 2015 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
