Neuropeptide Y Overexpression Using Recombinant Adenoassociated Viral Vectors

Francesco Noé, Angelisa Frasca, Claudia Balducci, Mirjana Carli, Gunther Sperk, Francesco Ferraguti, Asla Pitkänen, Ross Bland, Helen Fitzsimons, Matthew During, Annamaria Vezzani

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Gene therapy may represent a promising alternative treatment of epileptic patients who are resistant to conventional anti-epileptic drugs. Among the various approaches for the application of gene therapy in the treatment of CNS disorders, recombinant adeno-associated viral (AAV) vectors have been most widely used. Preclinical studies using a selection of "therapeutic" genes injected into the rodent brain to correct the compromised balance between inhibitory and excitatory transmission in epilepsy, showed significant reduction of seizures and inhibition of epileptogenesis. In particular, transduction of neuropeptide genes, such as galanin and neuropeptide Y (NPY) in specific brain areas in experimental models of seizures resulted in significant anticonvulsant effects. Recent findings showed a long-lasting NPY over-expression in the rat hippocampus by local application of recombinant AAV vectors associated with reduced generalization of seizures, delayed kindling epileptogenesis, and strong reduction of chronic spontaneous seizures. These results establish a proof-of-principle evidence of the efficacy of gene therapy as anticonvulsant treatment. Additional investigations are required to address safety concerns and possible side effects in more detail.

Original languageEnglish
Pages (from-to)300-306
Number of pages7
JournalNeurotherapeutics
Volume6
Issue number2
DOIs
Publication statusPublished - Apr 2009

Fingerprint

Neuropeptide Y
Seizures
Genetic Therapy
Anticonvulsants
Galanin
Brain
Therapeutics
Neuropeptides
Genes
Rodentia
Epilepsy
Hippocampus
Theoretical Models
Safety
Pharmaceutical Preparations

Keywords

  • Adeno-associated viral vectors
  • anticonvulsant
  • gene therapy in epilepsy
  • neuropeptides
  • temporal lobe epilepsy

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Clinical Neurology
  • Pharmacology

Cite this

Neuropeptide Y Overexpression Using Recombinant Adenoassociated Viral Vectors. / Noé, Francesco; Frasca, Angelisa; Balducci, Claudia; Carli, Mirjana; Sperk, Gunther; Ferraguti, Francesco; Pitkänen, Asla; Bland, Ross; Fitzsimons, Helen; During, Matthew; Vezzani, Annamaria.

In: Neurotherapeutics, Vol. 6, No. 2, 04.2009, p. 300-306.

Research output: Contribution to journalArticle

Noé, F, Frasca, A, Balducci, C, Carli, M, Sperk, G, Ferraguti, F, Pitkänen, A, Bland, R, Fitzsimons, H, During, M & Vezzani, A 2009, 'Neuropeptide Y Overexpression Using Recombinant Adenoassociated Viral Vectors', Neurotherapeutics, vol. 6, no. 2, pp. 300-306. https://doi.org/10.1016/j.nurt.2009.01.012
Noé, Francesco ; Frasca, Angelisa ; Balducci, Claudia ; Carli, Mirjana ; Sperk, Gunther ; Ferraguti, Francesco ; Pitkänen, Asla ; Bland, Ross ; Fitzsimons, Helen ; During, Matthew ; Vezzani, Annamaria. / Neuropeptide Y Overexpression Using Recombinant Adenoassociated Viral Vectors. In: Neurotherapeutics. 2009 ; Vol. 6, No. 2. pp. 300-306.
@article{b656e0ae17ce4dac8a5aa92e8ff29045,
title = "Neuropeptide Y Overexpression Using Recombinant Adenoassociated Viral Vectors",
abstract = "Gene therapy may represent a promising alternative treatment of epileptic patients who are resistant to conventional anti-epileptic drugs. Among the various approaches for the application of gene therapy in the treatment of CNS disorders, recombinant adeno-associated viral (AAV) vectors have been most widely used. Preclinical studies using a selection of {"}therapeutic{"} genes injected into the rodent brain to correct the compromised balance between inhibitory and excitatory transmission in epilepsy, showed significant reduction of seizures and inhibition of epileptogenesis. In particular, transduction of neuropeptide genes, such as galanin and neuropeptide Y (NPY) in specific brain areas in experimental models of seizures resulted in significant anticonvulsant effects. Recent findings showed a long-lasting NPY over-expression in the rat hippocampus by local application of recombinant AAV vectors associated with reduced generalization of seizures, delayed kindling epileptogenesis, and strong reduction of chronic spontaneous seizures. These results establish a proof-of-principle evidence of the efficacy of gene therapy as anticonvulsant treatment. Additional investigations are required to address safety concerns and possible side effects in more detail.",
keywords = "Adeno-associated viral vectors, anticonvulsant, gene therapy in epilepsy, neuropeptides, temporal lobe epilepsy",
author = "Francesco No{\'e} and Angelisa Frasca and Claudia Balducci and Mirjana Carli and Gunther Sperk and Francesco Ferraguti and Asla Pitk{\"a}nen and Ross Bland and Helen Fitzsimons and Matthew During and Annamaria Vezzani",
year = "2009",
month = "4",
doi = "10.1016/j.nurt.2009.01.012",
language = "English",
volume = "6",
pages = "300--306",
journal = "Neurotherapeutics",
issn = "1933-7213",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - Neuropeptide Y Overexpression Using Recombinant Adenoassociated Viral Vectors

AU - Noé, Francesco

AU - Frasca, Angelisa

AU - Balducci, Claudia

AU - Carli, Mirjana

AU - Sperk, Gunther

AU - Ferraguti, Francesco

AU - Pitkänen, Asla

AU - Bland, Ross

AU - Fitzsimons, Helen

AU - During, Matthew

AU - Vezzani, Annamaria

PY - 2009/4

Y1 - 2009/4

N2 - Gene therapy may represent a promising alternative treatment of epileptic patients who are resistant to conventional anti-epileptic drugs. Among the various approaches for the application of gene therapy in the treatment of CNS disorders, recombinant adeno-associated viral (AAV) vectors have been most widely used. Preclinical studies using a selection of "therapeutic" genes injected into the rodent brain to correct the compromised balance between inhibitory and excitatory transmission in epilepsy, showed significant reduction of seizures and inhibition of epileptogenesis. In particular, transduction of neuropeptide genes, such as galanin and neuropeptide Y (NPY) in specific brain areas in experimental models of seizures resulted in significant anticonvulsant effects. Recent findings showed a long-lasting NPY over-expression in the rat hippocampus by local application of recombinant AAV vectors associated with reduced generalization of seizures, delayed kindling epileptogenesis, and strong reduction of chronic spontaneous seizures. These results establish a proof-of-principle evidence of the efficacy of gene therapy as anticonvulsant treatment. Additional investigations are required to address safety concerns and possible side effects in more detail.

AB - Gene therapy may represent a promising alternative treatment of epileptic patients who are resistant to conventional anti-epileptic drugs. Among the various approaches for the application of gene therapy in the treatment of CNS disorders, recombinant adeno-associated viral (AAV) vectors have been most widely used. Preclinical studies using a selection of "therapeutic" genes injected into the rodent brain to correct the compromised balance between inhibitory and excitatory transmission in epilepsy, showed significant reduction of seizures and inhibition of epileptogenesis. In particular, transduction of neuropeptide genes, such as galanin and neuropeptide Y (NPY) in specific brain areas in experimental models of seizures resulted in significant anticonvulsant effects. Recent findings showed a long-lasting NPY over-expression in the rat hippocampus by local application of recombinant AAV vectors associated with reduced generalization of seizures, delayed kindling epileptogenesis, and strong reduction of chronic spontaneous seizures. These results establish a proof-of-principle evidence of the efficacy of gene therapy as anticonvulsant treatment. Additional investigations are required to address safety concerns and possible side effects in more detail.

KW - Adeno-associated viral vectors

KW - anticonvulsant

KW - gene therapy in epilepsy

KW - neuropeptides

KW - temporal lobe epilepsy

UR - http://www.scopus.com/inward/record.url?scp=62949159436&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=62949159436&partnerID=8YFLogxK

U2 - 10.1016/j.nurt.2009.01.012

DO - 10.1016/j.nurt.2009.01.012

M3 - Article

VL - 6

SP - 300

EP - 306

JO - Neurotherapeutics

JF - Neurotherapeutics

SN - 1933-7213

IS - 2

ER -