Direct Intracerebral Nerve Growth Factor Gene Transfer Using a Recombinant Adenovirus: Effect on Basal Forebrain Cholinergic Neurons during Aging

Castel-Barthe, M.N.; Jazat-Poindessous, F.; Barnéoud, Pascal; Vigne, Emmanuelle; Revah, Frédéric; Mallet, Jacques; Lamour, Y.

doi:10.1006/nbdi.1996.0008

Cited by 42 publications

(13 citation statements)

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“…A herpes simplex vims has been used to deUver NGF to peripheral sympathetic neurons and shown to prevent the decUne in tyrosine hydroxylase following denervation (Federoff et al, 1992). An adenovims has also been used to deUver NGF to cholinergic basal forebrain neurons in aged rats (Castel-Barthe et al, 1996). Our recent smdies show that adenovkus can be used to deUver ttophic support to dopaminergic neurons ki the CNS in an animal model of Parkinson's disease (Choi-Lundberg et al, 1997).…”

Section: Discussionmentioning

confidence: 97%

Human Fetal Astrocytes as anEx VivoGene Therapy Vehicle for Delivering Biologically Active Nerve Growth Factor

Lin¹,

Cunningham²,

Epstein³

et al. 1997

Human Gene Therapy

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The therapeutic use of neurotrophic factors for neurodegenerative diseases is promising, however, optimal methods for continuous delivery of these substances to the human central nervous system (CNS) remains problematic. One approach would be to graft genetically engineered human cells that continuously secrete high levels of a biologically produced and processed neurotrophic factor. This ex vivo gene therapy approach has worked well in animal models of neurodegenerative diseases using a variety of nonneuronal cell types to deliver the transgene. In our studies, we have been investigating the potential of astrocytes, a cell type normally present in the CNS, as a vehicle for ex vivo gene therapy. Here, we demonstrate that astrocytes in the human fetal cortex can be isolated and efficiently infected with an amphotropic retrovirus harboring mouse beta-nerve growth factor (NGF). These transduced astrocytes express high levels of NGF mRNA and secrete bioactive NGF protein as demonstrated by stimulation of neurite outgrowth from adrenal chromaffin cells. NGF ELISA showed that these astrocytes secrete NGF protein at a rate of 41 ng/day per 10(5) cells after 2 weeks in vitro, whereas NGF is undetectable in medium conditioned by normal astrocytes. These data suggest that human fetal astrocytes can be used for delivering biologically produced neurotrophic factors to the human CNS.

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Section: Discussionmentioning

confidence: 97%

Human Fetal Astrocytes as anEx VivoGene Therapy Vehicle for Delivering Biologically Active Nerve Growth Factor

Lin¹,

Cunningham²,

Epstein³

et al. 1997

Human Gene Therapy

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show abstract

“…6,7,11,19,[42][43][44][45][46] Exogenous administration with NGF has been shown to spare septal cholinergic neurons from death and degeneration following injury. [1][2][3]47 NGF increases ChAT activity both in vitro 32,48 and in intact animals.…”

Section: Figure 2 Ngf Gene Transfectio In Vitro (A) Increases In Ngfmentioning

confidence: 99%

“…During the past few years, significant progress has been made in the development of techniques for transfecting genes into the CNS and exploring their potential to treat CNS disorders. [13][14][15][16][17][18][19][20][21][22] Cationic liposomes, which can condense DNA and increase transfection efficiency both in vitro and in vivo, [23][24][25][26][27][28][29] have several attractive features as vectors for gene transfer. First, cationic liposomes are non-immunogenic and nontoxic at therapeutic doses.…”

Section: Introductionmentioning

confidence: 99%

Liposome-mediated NGF gene transfection following neuronal injury: potential therapeutic applications

et al. 1999

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We have systematically investigated the therapeutic potenine acetyltransferase (ChAT) activity in cultures following tial of cationic liposome-mediated neurotrophic gene transcalcium-dependent depolarization injury. In in vivo studies, fer for treatment of CNS injury. Following determination of following intraventricular injections of NGF cDNA comoptimal transfection conditions, we examined the effects of plexed with DC-Chol liposomes, ELISA detected nine-to dimethylaminoethane-carbamoyl-cholesterol (DC-Chol) 12-fold increases of NGF in rat CSF. Further studies liposome-mediated NGF cDNA transfection in injured and showed that liposome/NGF cDNA complexes could attenuuninjured primary septo-hippocampal cell cultures and rat ate the loss of cholinergic neuronal immunostaining in the brains. In in vitro studies, we detected an increase of NGF rat septum after traumatic brain injury (TBI). Since deficits mRNA in cultures 1 day after transfection. Subsequent in cholinergic neurotransmission are a major consequence ELISA and PC12 cell biological assays confirmed that culof TBI, our studies demonstrate for the first time that DCtured cells secreted soluble active NGF into the media from Chol liposome-mediated NGF gene transfection may have day 2 after gene transfection. Further experiments showed therapeutic potential for treatment of brain injury. that such NGF gene transfection reduced the loss of chol-

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“…The history of efficient brain gene transfer begins with herpes virus vectors (Geller and Breakefield 1988; Federoff et al 1992; During et al 1994) and later adenovirus vectors (Le Gal La Salle et al 1993; Horellou et al 1994; Castel-Barthe et al 1996; Bilang-Bleuel et al 1997; Choi-Lundberg et al 1997). Efficiency and longevity of gene expression improved significantly with the subsequent advent of adeno-associated virus (AAV) (Kaplitt et al 1994; McCown et al 1996) (Fig.…”

Section: Vector Technologymentioning

confidence: 99%

Versatile Somatic Gene Transfer for Modeling Neurodegenerative Diseases

2009

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A growing variety of technical approaches allow control over the expression of selected genes in living organisms. The ability to deliver functional exogenous genes involved in neurodegenerative diseases has opened pathological processes to experimental analysis and targeted therapeutic development in rodent and primate pre-clinical models. Biological adaptability, economic animal use, and reduced model development costs complement improved control over spatial and temporal gene expression compared with conventional transgenic models. A review of viral vector studies, typically adeno-associated virus or lentivirus, for expression of three proteins that are central to major neurodegenerative diseases, will illustrate how this approach has powered new advances and opportunities in CNS disease research.

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Direct Intracerebral Nerve Growth Factor Gene Transfer Using a Recombinant Adenovirus: Effect on Basal Forebrain Cholinergic Neurons during Aging

Cited by 42 publications

References 0 publications

Human Fetal Astrocytes as anEx VivoGene Therapy Vehicle for Delivering Biologically Active Nerve Growth Factor

Human Fetal Astrocytes as anEx VivoGene Therapy Vehicle for Delivering Biologically Active Nerve Growth Factor

Liposome-mediated NGF gene transfection following neuronal injury: potential therapeutic applications

Versatile Somatic Gene Transfer for Modeling Neurodegenerative Diseases

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