PMID- 16364693
OWN - NLM
STAT- MEDLINE
DCOM- 20070731
LR  - 20180101
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 13
IP  - 3
DP  - 2006 Mar
TI  - CNS-directed AAV2-mediated gene therapy ameliorates functional deficits in a 
      murine model of infantile neuronal ceroid lipofuscinosis.
PG  - 538-47
AB  - The neuronal ceroid lipofuscinoses (Batten disease) are a group of inherited 
      neurodegenerative diseases characterized by the progressive intralysosomal 
      accumulation of autofluorescent material in many cells, visual defects, seizures, 
      cognitive deficits, and premature death. Infantile neuronal ceroid lipofuscinosis 
      (INCL) has the earliest onset ( approximately 1.5 years of age) and is caused by 
      a deficiency in the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1). 
      Currently there is no effective treatment for children with INCL. In this study, 
      newborn PPT1-deficient mice received two (cortex), four (cortex and hippocampus), 
      or six (cortex, hippocampus, and cerebellum) bilateral intracranial injections of 
      AAV2-PPT1. The AAV-treated animals had localized increases in PPT1 activity, 
      decreased autofluorescent material, improved histologic parameters, and increased 
      brain mass. In addition, the treated animals had dose-dependent improvements in a 
      battery of behavioral tests and improved interictal electroencephalographic 
      tracings. However, there was neither a significant decrease in seizure frequency 
      nor an increase in longevity even in INCL animals receiving six injections. These 
      data suggest that early treatment of INCL using gene transfer techniques can be 
      efficacious. However, higher levels or a broader distribution of PPT1 expression, 
      or both, will be required for more complete correction of this neurodegenerative 
      disease.
FAU - Griffey, Megan A
AU  - Griffey MA
AD  - Department of Internal Medicine, Washington University School of Medicine, St. 
      Louis, MO 63110, USA.
FAU - Wozniak, David
AU  - Wozniak D
FAU - Wong, Michael
AU  - Wong M
FAU - Bible, Ellen
AU  - Bible E
FAU - Johnson, Kendra
AU  - Johnson K
FAU - Rothman, Steven M
AU  - Rothman SM
FAU - Wentz, Annie E
AU  - Wentz AE
FAU - Cooper, Jonathan D
AU  - Cooper JD
FAU - Sands, Mark S
AU  - Sands MS
LA  - eng
GR  - NS043205/NS/NINDS NIH HHS/United States
GR  - NS41930/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20051220
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Membrane Proteins)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (PPT1 protein, human)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
SB  - IM
MH  - Animals
MH  - Brain/metabolism/*physiology/virology
MH  - Child
MH  - Child, Preschool
MH  - Dependovirus/*genetics/physiology
MH  - Disease Models, Animal
MH  - *Genetic Therapy
MH  - Genetic Vectors/physiology/*therapeutic use
MH  - Humans
MH  - Longevity
MH  - Membrane Proteins/administration & dosage/biosynthesis/genetics
MH  - Mice
MH  - Mice, Knockout
MH  - Neuronal Ceroid-Lipofuscinoses/enzymology/genetics/*physiopathology/*therapy
MH  - Thiolester Hydrolases/deficiency/genetics
EDAT- 2005/12/21 09:00
MHDA- 2007/08/01 09:00
CRDT- 2005/12/21 09:00
PHST- 2005/07/26 00:00 [received]
PHST- 2005/10/31 00:00 [revised]
PHST- 2005/11/02 00:00 [accepted]
PHST- 2005/12/21 09:00 [pubmed]
PHST- 2007/08/01 09:00 [medline]
PHST- 2005/12/21 09:00 [entrez]
AID - S1525-0016(05)01699-0 [pii]
AID - 10.1016/j.ymthe.2005.11.008 [doi]
PST - ppublish
SO  - Mol Ther. 2006 Mar;13(3):538-47. doi: 10.1016/j.ymthe.2005.11.008. Epub 2005 Dec 
      20.