Transgene Expression, Bioactivity, and Safety of CERE-120 (AAV2-Neurturin) Following Delivery to the Monkey Striatum.

Transgene Expression, Bioactivity, and Safety of CERE-120 (AAV2-Neurturin) Following Delivery to the Monkey Striatum. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Transgene Expression, Bioactivity, and Safety of CERE-120 (AAV2-Neurturin) Following Delivery to the Monkey Striatum. Abstract Text:

Neurturin (NTN) is a neurotrophic factor for dopaminergic neurons that may be therapeutic for patients with Parkinson's disease (PD). As a crucial component in a series of nonclinical translational studies aimed at testing whether CERE-120 should advance into clinical trials in PD subjects, we characterized the expression, bioactivity and safety of CERE-120, an adeno-associated virus type-2 (AAV2) vector encoding NTN, following delivery to the striatum of nonhuman primates. Monkeys received bilateral injections of CERE-120 across a tenfold range of doses (6 x 10(10) to 6 x 10(11) vector genomes per animal) or formulation buffer (FB) control. We report here, for the first time, a dose-related: increase in NTN protein expression within the striatum and substantia nigra (SN) pars compacta of nonhuman primates; increase in nigrostriatal tyrosine hydroxylase (TH), (the rate-limited enzyme for dopamine); and activation of phosphorylated signal-regulated kinase (a common neurotrophic signaling event). Additionally, extensive toxicology testing revealed no adverse effects of CERE-120 on in-life measures, neurotoxicity (in any site throughout the brain) or systemic pathology (in any organ or tissue) across the tenfold range of doses. Collectively, these data provide substantial novel evidence for the potential utility of CERE-120 as a novel treatment for PD and support ongoing clinical trials testing CERE-120 in PD patients.Molecular Therapy (2008) 16 10, 1737-1744 doi:10.1038/mt.2008.170.

Transgene Expression, Bioactivity, and Safety of CERE-120 (AAV2-Neurturin) Following Delivery to the Monkey Striatum. Publishing Authors By Initials

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Transgene Expression, Bioactivity, and Safety of CERE-120 (AAV2-Neurturin) Following Delivery to the Monkey Striatum. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Molecular therapy : the journal of the American So

VOLUME: 16

Page Numbers: 1737-44

Journal Abbreviation: Mol. Ther.

ISSN: 1525-0024

DAY: 26

MONTH: 08

YEAR: 2008

Transgene Expression, Bioactivity, and Safety of CERE-120 (AAV2-Neurturin) Following Delivery to the Monkey Striatum. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100890581

Transgene Expression, Bioactivity, and Safety of CERE-120 (AAV2-Neurturin) Following Delivery to the Monkey Striatum. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Transgene Expression, Bioactivity, and Safety of CERE-120 (AAV2-Neurturin) Following Delivery to the Monkey Striatum. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Transgene Expression, Bioactivity, and Safety of CERE-120 (AAV2-Neurturin) Following Delivery to the Monkey Striatum.

AFFILIATION: 1Ceregene, Inc., San Diego, California, USA.

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Mol Ther

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Transgene Expression, Bioactivity, and Safety of CERE-120 AAV2-Neurturin Following Delivery to the Monkey Striatum Related Publications

• A visual recognition memory test for the assessment of cognitive function in aging and dementia.
• Age differences in the vulnerability of facial recognition memory to proactive interference.
• Age-related differences in behavior across the life span of the C57BL/6J mouse.
• Equivalent spatial-rotation deficits in normal aging and Alzheimer's disease.
• Four stimulants of the central nervous system: effects on short-term memory in young versus aged monkeys.
• Pseudoaneurysm of the inferior epigastric artery: diagnosis and percutaneous treatment.
• Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2-neurturin) to patients with idiopathic Parkinson's disease: an open-label, phase I trial.
• Striatal Delivery of Neurturin by CERE-120, an AAV2 Vector for the Treatment of Dopaminergic Neuron Degeneration in Parkinson's Disease.
• Therapeutic potential of CERE-110 (AAV2-NGF): Targeted, stable, and sustained NGF delivery and trophic activity on rodent basal forebrain cholinergic neurons.
• Transgene Expression, Bioactivity, and Safety of CERE-120 (AAV2-Neurturin) Following Delivery to the Monkey Striatum.
• Ultrastructure of immediate microvascular lung injury induced by bacterial endotoxin in the isolated, no-deficient lung perfused with full blood.