Distribution of AAV2-hAADC-transduced cells after 3 years in Parkinsonian monkeys

Marcel M. Daadi; Phillip Pivirotto; John Bringas; Janet Cunningham; John Forsayeth; Jamie Eberling; Krys S. Bankiewicz

doi:10.1097/01.wnr.0000198952.38563.05

Distribution of AAV2-hAADC-transduced cells after 3 years in Parkinsonian monkeys

Marcel M. Daadi, Phillip Pivirotto, John Bringas, Janet Cunningham, John Forsayeth, Jamie Eberling, Krys S. Bankiewicz

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

The present report describes for the first time, the stability of recombinant adeno-associated virus serotype 2 (AAV2) human aromatic L-amino acid decarboxylase (hAADC) gene transfer after 3-year survival time in a non-human primate model of Parkinson's disease. 1-Methyl-4-phenyl-1,2,3,6- tetrahydropyridine-lesioned monkeys were treated with six injections of 30 μl/site of AAV2-hAADC at a concentration of 2 × 10¹² vg/ml into the caudate and putamen. Stereological analysis revealed a 46.6% increase in the total number of AAV2-hAADC-transduced cells in the striatum between 8 weeks and 3 years after gene transfer survival time. In the 8-week animals, the distribution of the AADC + cells was dispersed and heterogeneous, whereas in the 3-year animals it was widespread and homogenous. Confocal analysis demonstrated that approximately 85% of the AADC+ cells were neuronal nuclei immunoreactive.

Original language	English (US)
Pages (from-to)	201-204
Number of pages	4
Journal	NeuroReport
Volume	17
Issue number	2
DOIs	https://doi.org/10.1097/01.wnr.0000198952.38563.05
State	Published - Feb 2006
Externally published	Yes

Keywords

Gene therapy
Long-term gene transfer
Monkey MPTP
Parkinson's disease
Recombinant adeno-associated virus serotype 2
Stereology

ASJC Scopus subject areas

General Neuroscience

Access to Document

10.1097/01.wnr.0000198952.38563.05

Cite this

@article{ee6323fcbffe496190b1159f38fb608a,

title = "Distribution of AAV2-hAADC-transduced cells after 3 years in Parkinsonian monkeys",

abstract = "The present report describes for the first time, the stability of recombinant adeno-associated virus serotype 2 (AAV2) human aromatic L-amino acid decarboxylase (hAADC) gene transfer after 3-year survival time in a non-human primate model of Parkinson's disease. 1-Methyl-4-phenyl-1,2,3,6- tetrahydropyridine-lesioned monkeys were treated with six injections of 30 μl/site of AAV2-hAADC at a concentration of 2 × 1012 vg/ml into the caudate and putamen. Stereological analysis revealed a 46.6% increase in the total number of AAV2-hAADC-transduced cells in the striatum between 8 weeks and 3 years after gene transfer survival time. In the 8-week animals, the distribution of the AADC + cells was dispersed and heterogeneous, whereas in the 3-year animals it was widespread and homogenous. Confocal analysis demonstrated that approximately 85% of the AADC+ cells were neuronal nuclei immunoreactive.",

keywords = "Gene therapy, Long-term gene transfer, Monkey MPTP, Parkinson's disease, Recombinant adeno-associated virus serotype 2, Stereology",

author = "Daadi, {Marcel M.} and Phillip Pivirotto and John Bringas and Janet Cunningham and John Forsayeth and Jamie Eberling and Bankiewicz, {Krys S.}",

year = "2006",

month = feb,

doi = "10.1097/01.wnr.0000198952.38563.05",

language = "English (US)",

volume = "17",

pages = "201--204",

journal = "NeuroReport",

issn = "0959-4965",

publisher = "Lippincott Williams and Wilkins",

number = "2",

}

TY - JOUR

T1 - Distribution of AAV2-hAADC-transduced cells after 3 years in Parkinsonian monkeys

AU - Daadi, Marcel M.

AU - Pivirotto, Phillip

AU - Bringas, John

AU - Cunningham, Janet

AU - Forsayeth, John

AU - Eberling, Jamie

AU - Bankiewicz, Krys S.

PY - 2006/2

Y1 - 2006/2

N2 - The present report describes for the first time, the stability of recombinant adeno-associated virus serotype 2 (AAV2) human aromatic L-amino acid decarboxylase (hAADC) gene transfer after 3-year survival time in a non-human primate model of Parkinson's disease. 1-Methyl-4-phenyl-1,2,3,6- tetrahydropyridine-lesioned monkeys were treated with six injections of 30 μl/site of AAV2-hAADC at a concentration of 2 × 1012 vg/ml into the caudate and putamen. Stereological analysis revealed a 46.6% increase in the total number of AAV2-hAADC-transduced cells in the striatum between 8 weeks and 3 years after gene transfer survival time. In the 8-week animals, the distribution of the AADC + cells was dispersed and heterogeneous, whereas in the 3-year animals it was widespread and homogenous. Confocal analysis demonstrated that approximately 85% of the AADC+ cells were neuronal nuclei immunoreactive.

AB - The present report describes for the first time, the stability of recombinant adeno-associated virus serotype 2 (AAV2) human aromatic L-amino acid decarboxylase (hAADC) gene transfer after 3-year survival time in a non-human primate model of Parkinson's disease. 1-Methyl-4-phenyl-1,2,3,6- tetrahydropyridine-lesioned monkeys were treated with six injections of 30 μl/site of AAV2-hAADC at a concentration of 2 × 1012 vg/ml into the caudate and putamen. Stereological analysis revealed a 46.6% increase in the total number of AAV2-hAADC-transduced cells in the striatum between 8 weeks and 3 years after gene transfer survival time. In the 8-week animals, the distribution of the AADC + cells was dispersed and heterogeneous, whereas in the 3-year animals it was widespread and homogenous. Confocal analysis demonstrated that approximately 85% of the AADC+ cells were neuronal nuclei immunoreactive.

KW - Gene therapy

KW - Long-term gene transfer

KW - Monkey MPTP

KW - Parkinson's disease

KW - Recombinant adeno-associated virus serotype 2

KW - Stereology

UR - http://www.scopus.com/inward/record.url?scp=30744472931&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=30744472931&partnerID=8YFLogxK

U2 - 10.1097/01.wnr.0000198952.38563.05

DO - 10.1097/01.wnr.0000198952.38563.05

M3 - Article

C2 - 16407771

AN - SCOPUS:30744472931

SN - 0959-4965

VL - 17

SP - 201

EP - 204

JO - NeuroReport

JF - NeuroReport

IS - 2

ER -

Distribution of AAV2-hAADC-transduced cells after 3 years in Parkinsonian monkeys

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this