| Interventional MRI-guided Putaminal Delivery of AAV2-GDNF for a Planned Clinical Trial in Parkinson's Disease. | |
| | |
MedLine Citation:
|
PMID: 21343917 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Clinical trials involving direct infusion of neurotrophic therapies for Parkinson's disease (PD) have suffered from poor coverage of the putamen. The planned use of a novel interventional-magnetic resonance imaging (iMRI) targeting system for achieving precise, real-time convection-enhanced delivery in a planned clinical trial of adeno-associated virus serotype 2 (AAV2)-glial-derived neurotrophic factor (GDNF) in PD patients was modeled in nonhuman primates (NHP). NHP received bilateral coinfusions of gadoteridol (Gd)/AAV2-GDNF into two sites in each putamen, and three NHP received larger infusion volumes in the thalamus. The average targeting error for cannula tip placement in the putamen was <1 mm, and adjacent putamenal infusions were distributed in a uniform manner. GDNF expression patterns in the putamen were highly correlated with areas of Gd distribution seen on MRI. The distribution volume to infusion volume ratio in the putamen was similar to that in the thalamus, where larger infusions were achieved. Modeling the placement of adjacent 150 and 300 µl thalamic infusions into the three-dimensional space of the human putamen demonstrated coverage of the postcommissural putamen, containment within the striatum and expected anterograde transport to globus pallidus and substantia nigra pars reticulata. The results elucidate the necessary parameters for achieving widespread GDNF expression in the putamenal motor area and afferent substantia nigra of PD patients. |
| | |
Authors:
|
R Mark Richardson; Adrian P Kells; Kathryn H Rosenbluth; Ernesto Aguilar Salegio; Massimo S Fiandaca; Paul S Larson; Philip A Starr; Alastair J Martin; Russell R Lonser; Howard J Federoff; John R Forsayeth; Krystof S Bankiewicz |
Related Documents
:
|
11435037 - Spiral ct of the gastric carcinoma: staging and enhancement pattern. 7201577 - Maximizing the harvest of contrast enhancing lesions in multiple sclerosis. 16484347 - Hepatic metastases: detection with multi-detector row ct, spio-enhanced mr imaging, and... 7957287 - Dynamic gd-dota-enhanced mr imaging of hepatic metastases from pancreatic neuroendocrin... 18622607 - Mr findings in patients with disabling musculocutaneous chronic graft-versus-host disease. 17399807 - Pericardial synovial sarcoma mimicking pericarditis in findings of cardiac magnetic res... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-2-22 |
Journal Detail:
|
Title: Molecular therapy : the journal of the American Society of Gene Therapy Volume: - ISSN: 1525-0024 ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
|
Created Date: 2011-2-23 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 100890581 Medline TA: Mol Ther Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: "Same day" ex-vivo regional gene therapy: a novel strategy to enhance bone repair.
Next Document: The prognostic power of the NOD2 genotype for complicated Crohn's disease: a meta-analysis.