Adeno-associated virus 2-mediated gene therapy decreases autofluorescent storage material and increases brain mass in a murine model of infantile neuronal ceroid lipofuscinosis

Megan Griffey, Ellen Bible, Carole Vogler, Beth Levy, Praveena Gupta, Jonathan Cooper, Mark S. Sands

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Infantile neuronal ceroid lipofuscinosis (INCL) is the earliest onset form of a class of inherited neurodegenerative disease called Batten disease. INCL is caused by a deficiency in the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1). Autofluorescent storage material accumulates in virtually all tissues in INCL patients, including the brain, and leads to widespread neuronal loss and cortical atrophy. To determine the efficacy of viral-mediated gene therapy, we injected a recombinant adeno-associated virus 2 vector encoding human PPT1 (rAAV-PPT1) intracranially (I.C.) into a murine model of INCL. INCL mice given four I.C. injections of rAAV-PPT1 as newborns exhibited PPT1 activity near the injection sites and decreased secondary elevations of another lysosomal enzyme. In addition, storage material was decreased in cortical, hippocampal, and cerebellar neurons, and brain weights and cortical thicknesses were increased. These data demonstrate that an adeno-associated virus 2 (AAV2)-mediated gene therapy approach may provide some therapeutic benefit for INCL.

Original languageEnglish (US)
Pages (from-to)360-369
Number of pages10
JournalNeurobiology of Disease
Volume16
Issue number2
DOIs
StatePublished - Jul 2004
Externally publishedYes

Fingerprint

Neuronal Ceroid-Lipofuscinoses
Dependovirus
Genetic Therapy
Brain
Injections
Viral Genes
Enzymes
Ceroid lipofuscinosis, neuronal 1, infantile
Neurodegenerative Diseases
Atrophy
Newborn Infant
Neurons
Weights and Measures
palmitoyl-protein thioesterase

Keywords

  • Adeno-associated virus
  • Batten disease
  • Gene therapy
  • Infantile neuronal ceroid lipofuscinosis
  • Lysosomal storage disease
  • Neurodegenerative disease
  • Palmitoyl protein thioesterase

ASJC Scopus subject areas

  • Neurology

Cite this

Adeno-associated virus 2-mediated gene therapy decreases autofluorescent storage material and increases brain mass in a murine model of infantile neuronal ceroid lipofuscinosis. / Griffey, Megan; Bible, Ellen; Vogler, Carole; Levy, Beth; Gupta, Praveena; Cooper, Jonathan; Sands, Mark S.

In: Neurobiology of Disease, Vol. 16, No. 2, 07.2004, p. 360-369.

Research output: Contribution to journalArticle

@article{d9bc38ab5a914eebaadb63d267c429c7,
title = "Adeno-associated virus 2-mediated gene therapy decreases autofluorescent storage material and increases brain mass in a murine model of infantile neuronal ceroid lipofuscinosis",
abstract = "Infantile neuronal ceroid lipofuscinosis (INCL) is the earliest onset form of a class of inherited neurodegenerative disease called Batten disease. INCL is caused by a deficiency in the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1). Autofluorescent storage material accumulates in virtually all tissues in INCL patients, including the brain, and leads to widespread neuronal loss and cortical atrophy. To determine the efficacy of viral-mediated gene therapy, we injected a recombinant adeno-associated virus 2 vector encoding human PPT1 (rAAV-PPT1) intracranially (I.C.) into a murine model of INCL. INCL mice given four I.C. injections of rAAV-PPT1 as newborns exhibited PPT1 activity near the injection sites and decreased secondary elevations of another lysosomal enzyme. In addition, storage material was decreased in cortical, hippocampal, and cerebellar neurons, and brain weights and cortical thicknesses were increased. These data demonstrate that an adeno-associated virus 2 (AAV2)-mediated gene therapy approach may provide some therapeutic benefit for INCL.",
keywords = "Adeno-associated virus, Batten disease, Gene therapy, Infantile neuronal ceroid lipofuscinosis, Lysosomal storage disease, Neurodegenerative disease, Palmitoyl protein thioesterase",
author = "Megan Griffey and Ellen Bible and Carole Vogler and Beth Levy and Praveena Gupta and Jonathan Cooper and Sands, {Mark S.}",
year = "2004",
month = "7",
doi = "10.1016/j.nbd.2004.03.005",
language = "English (US)",
volume = "16",
pages = "360--369",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Adeno-associated virus 2-mediated gene therapy decreases autofluorescent storage material and increases brain mass in a murine model of infantile neuronal ceroid lipofuscinosis

AU - Griffey, Megan

AU - Bible, Ellen

AU - Vogler, Carole

AU - Levy, Beth

AU - Gupta, Praveena

AU - Cooper, Jonathan

AU - Sands, Mark S.

PY - 2004/7

Y1 - 2004/7

N2 - Infantile neuronal ceroid lipofuscinosis (INCL) is the earliest onset form of a class of inherited neurodegenerative disease called Batten disease. INCL is caused by a deficiency in the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1). Autofluorescent storage material accumulates in virtually all tissues in INCL patients, including the brain, and leads to widespread neuronal loss and cortical atrophy. To determine the efficacy of viral-mediated gene therapy, we injected a recombinant adeno-associated virus 2 vector encoding human PPT1 (rAAV-PPT1) intracranially (I.C.) into a murine model of INCL. INCL mice given four I.C. injections of rAAV-PPT1 as newborns exhibited PPT1 activity near the injection sites and decreased secondary elevations of another lysosomal enzyme. In addition, storage material was decreased in cortical, hippocampal, and cerebellar neurons, and brain weights and cortical thicknesses were increased. These data demonstrate that an adeno-associated virus 2 (AAV2)-mediated gene therapy approach may provide some therapeutic benefit for INCL.

AB - Infantile neuronal ceroid lipofuscinosis (INCL) is the earliest onset form of a class of inherited neurodegenerative disease called Batten disease. INCL is caused by a deficiency in the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1). Autofluorescent storage material accumulates in virtually all tissues in INCL patients, including the brain, and leads to widespread neuronal loss and cortical atrophy. To determine the efficacy of viral-mediated gene therapy, we injected a recombinant adeno-associated virus 2 vector encoding human PPT1 (rAAV-PPT1) intracranially (I.C.) into a murine model of INCL. INCL mice given four I.C. injections of rAAV-PPT1 as newborns exhibited PPT1 activity near the injection sites and decreased secondary elevations of another lysosomal enzyme. In addition, storage material was decreased in cortical, hippocampal, and cerebellar neurons, and brain weights and cortical thicknesses were increased. These data demonstrate that an adeno-associated virus 2 (AAV2)-mediated gene therapy approach may provide some therapeutic benefit for INCL.

KW - Adeno-associated virus

KW - Batten disease

KW - Gene therapy

KW - Infantile neuronal ceroid lipofuscinosis

KW - Lysosomal storage disease

KW - Neurodegenerative disease

KW - Palmitoyl protein thioesterase

UR - http://www.scopus.com/inward/record.url?scp=2942588715&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2942588715&partnerID=8YFLogxK

U2 - 10.1016/j.nbd.2004.03.005

DO - 10.1016/j.nbd.2004.03.005

M3 - Article

C2 - 15193292

AN - SCOPUS:2942588715

VL - 16

SP - 360

EP - 369

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

IS - 2

ER -