Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Successful PGD for late infantile neuronal ceroid lipofuscinosis achieved by combined chromosome and TPP1 gene analysis.
|
23768618 |
2013 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
Biomarker
|
disease |
BEFREE |
TPP1, encoding the tripeptidyl-peptidase 1 enzyme, is known as the causative gene for late infantile neuronal ceroid lipofuscinosis disease 2 (CLN2 disease).
|
23418007 |
2013 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
Biomarker
|
disease |
BEFREE |
Our prior studies showed that delivery of the human CLN2 cDNA directly to the CNS, using an adeno-associated virus serotype 2 (AAV2) vector, is safe in children with LINCL.
|
23131032 |
2012 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
Biomarker
|
disease |
BEFREE |
These results demonstrate for the first time in a large animal model of LINCL widespread delivery of biochemically active TPP1 to the brain after IT administration along with a decrease in lysosomal storage material.
|
21784683 |
2011 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
Biomarker
|
disease |
BEFREE |
The authors conducted a phase I study of late infantile neuronal ceroid lipofuscinosis using an adenoassociated virus serotype 2 (AAV2) vector containing the deficient CLN2 gene (AAV2(CU)hCLN2).
|
20672930 |
2010 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
Biomarker
|
disease |
BEFREE |
There are 35 missense mutations among 68 different mutations in the TPP1 gene, which encodes tripeptidyl peptidase I (TPPI), a lysosomal aminopeptidase associated with classic late-infantile neuronal ceroid lipofuscinosis (CLN2 disease).
|
20340139 |
2010 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
Biomarker
|
disease |
BEFREE |
Tripeptidyl aminopeptidase I (TPPI) is a crucial lysosomal enzyme that is deficient in the fatal neurodegenerative disorder called classic late-infantile neuronal ceroid lipofuscinosis (LINCL).
|
20689811 |
2010 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
These data provide new insights into TPP1 function and represent a valuable resource for constructing improved TPP1 variants for treatment of late infantile neuronal ceroid lipofuscinosis.
|
19038967 |
2009 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
28 disease-causing missense mutations are analyzed in the light of the TPP1 structure providing insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis.
|
19038966 |
2009 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
Biomarker
|
disease |
BEFREE |
Subsequently, we tested if intraventricular delivery of TPP1 to the LINCL mouse was efficacious.
|
18362923 |
2008 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
Biomarker
|
disease |
MGD |
Residual levels of tripeptidyl-peptidase I activity dramatically ameliorate disease in late-infantile neuronal ceroid lipofuscinosis.
|
18343701 |
2008 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
Biomarker
|
disease |
BEFREE |
A total average dose of 2.5 10(12) particle units of an adeno-associated virus (AAV) serotype 2 vector expressing the human CLN2 cDNA (AAV2 CU h-CLN2) was administered to 12 locations in the CNS of 10 children with LINCL.
|
18473686 |
2008 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Most of the patients, 9 of 11 (81.8%), were CLN2 type (late-infantile neuronal ceroid lipofuscinosis or Jansky-Bielschowsky), and 2 patients were the atypical type.
|
17690061 |
2007 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Mutations in tripeptidyl-peptidase I (TPP I) underlie the classic late-infantile form of neuronal ceroid lipofuscinoses (CLN2), the most common neurodegenerative disorders of childhood.
|
16895480 |
2006 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
AlteredExpression
|
disease |
BEFREE |
This study demonstrates that AAV-mediated TPP1 enzyme replacement corrects the hallmark cellular pathologies of cLINCL in the mouse model and raises the possibility of using AAV gene therapy to treat cLINCL patients.
|
16452657 |
2006 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
AlteredExpression
|
disease |
BEFREE |
In vitro studies demonstrated that AAV2CUhCLN2 expressed CLN2 and produced biologically active TPP-I protein of which a fraction was secreted as the pro-TPP-I precursor and was taken up by nontransduced cells (ie, cross-correction).
|
16052206 |
2005 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
Biomarker
|
disease |
BEFREE |
To assess this concept, an adeno-associated virus vector (AAV2CUh-CLN2) will be used to transfer to and express the human CLN2 cDNA in the brain of children with LINCL.
|
15610613 |
2004 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
Biomarker
|
disease |
BEFREE |
Mutations in classical late infantile neuronal ceroid lipofuscinosis disrupt transport of tripeptidyl-peptidase I to lysosomes.
|
15317752 |
2004 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
Biomarker
|
disease |
MGD |
A mouse model of classical late-infantile neuronal ceroid lipofuscinosis based on targeted disruption of the CLN2 gene results in a loss of tripeptidyl-peptidase I activity and progressive neurodegeneration.
|
15483130 |
2004 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
Biomarker
|
disease |
BEFREE |
Late infantile neuronal ceroid lipofuscinosis (LINCL) is caused by the deficiency of the lysosomal tripeptidyl peptidase-I encoded by CLN2.
|
14736728 |
2004 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
Biomarker
|
disease |
BEFREE |
Our results indicate the feasibility of vector-mediated gene transfer of TPP-I to the CNS as a potential therapy for LINCL.
|
12525835 |
2003 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
R208X mutation in CLN2 gene associated with reduced cerebrospinal fluid pterins in a girl with classic late infantile neuronal ceroid lipofuscinosis.
|
12950156 |
2003 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
Biomarker
|
disease |
BEFREE |
Our laboratory has developed a diagnostic service for classical late infantile neuronal ceroid lipofuscinosis (LINCL) by assay of tripeptidyl-peptidase I (TPP-I) activity using the fluorogenic peptide substrate Ala-Ala-Phe aminomethylcoumarin, followed by a screen for three mutations in the CLN2 gene.
|
11588997 |
2001 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
AlteredExpression
|
disease |
BEFREE |
The expression of unequivocal TPP-I deficiency in CV demonstrates that enzyme assay is a reliable option for prenatal diagnosis of LINCL.
|
11241534 |
2001 |
Late-Infantile Neuronal Ceroid Lipfuscinosis
|
0.800 |
Biomarker
|
disease |
BEFREE |
An assay for the CLN2p/TPP-I based on the cleavage of amino terminal tripeptide from G-F-F-L-AFC was applied to prenatal and postnatal diagnosis of LINCL patients and heterozygote carriers.
|
11589010 |
2001 |