Aspartoacylase Deficiency: The Enzyme Defect in Canavan Disease

Matalon, Reuben; Kaul, Rajinder; Casanova, J.; Michals, K.; Johnson, Anne B.; Rapin, Isabelle; Gashkoff, P.; Deanching, M.

doi:10.1007/bf03335413

Cited by 63 publications

(14 citation statements)

References 5 publications

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“…This leads to an accumulation of Nacetylaspartate (NAA) which impairs normal myelination and results in spongiform degeneration of the brain [90]. An adeno-associated virus (AAV-2) containing the human ASPA cDNA, a human neuron-specific enolase promoter and a post-transcriptional regulatory element were used to supplement the enzymatic activity in the brain [91].…”

Section: Aspartoacylase (Aspa) In Canavan Diseasementioning

confidence: 99%

Viral vectors as tools to model and treat neurodegenerative disorders

Déglon

Hantraye

2005

The Journal of Gene Medicine

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The identification of disease-causing genes in familial forms of neurodegenerative disorders and the development of genetic models closely replicating human central nervous system (CNS) pathologies have drastically changed our understanding of the molecular events leading to neuronal cell death. If these achievements open new opportunities of therapeutic interventions, including gene-based therapies, the presence of the blood-brain barrier and the post-mitotic and poor regenerative nature of the target cells constitute important challenges. Efficient delivery systems taking into account the specificity of the CNS are required to administer potential therapeutic candidates. In addition, genetic models in large animals that replicate the late stages of the diseases are in most cases not available for pre-clinical studies. The present review summarizes the potential of viral vectors as tools to create new genetic models of CNS disorders in various species including primates and the recent progress toward viral gene therapy clinical trials for the administration of therapeutic candidates into the brain.

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Section: Aspartoacylase (Aspa) In Canavan Diseasementioning

confidence: 99%

Viral vectors as tools to model and treat neurodegenerative disorders

Déglon

Hantraye

2005

The Journal of Gene Medicine

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“…The basic biochemical defect is the deficiency of enzyme aspartoacylase (ASPA) (Matalon et al, 1988). More than 145 patients with CD have been diagnosed at our center alone during the past 5 years, and most of these patients are of Ashkenazi Jewish descent (Matalon et al, 1989. However, patients with CD have been diagnosed from other ethnic backgrounds (Banker and Victor, 1979; Matalon et al, 1993;Ozand et al, 1990).…”

Section: Introductionmentioning

confidence: 98%

Novel (cys152>arg) missense mutation in an Arab patient with Canavan disease

et al. 1995

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“…This biological marker is pathognomonic for CD and is useful for differentiation of this disease from other leukodystrophies (Matalon et al, 1989). NAA is a polar dicarboxylic acid with low extraction efficiency in common organic solvents.…”

Section: Introductionmentioning

confidence: 99%

Stable isotope dilution analysis of N‐acetylaspartic acid in urine by liquid chromatography electrospray ionization tandem mass spectrometry

Al-Dirbashi

Rashed

Al-Mokhadab

et al. 2007

Biomedical Chromatography

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N-acetylaspartic acid (NAA) is a specific urinary marker for Canavan disease, an autosomal recessive leukodystrophy. We developed a 'dilute and shoot' stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) method for determination of NAA in urine. Deuterated internal standard d(3)-NAA was added to untreated urine and the mixture was injected into the LC-MS/MS system operated in the negative ion mode. Chromatography was carried out on a C(8) minibore column using 50% acetonitrile solution containing 0.05% formic acid at a flow rate of 0.25 mL/min. The retention time was 1.6 min and the turnaround time was 2.2 min. NAA and d(3)-NAA were analyzed in multiple reaction monitoring mode. Calibrators and quality control samples were prepared in pooled control urine. The assay was linear up to 2000 micromol/L with limit of quantification at 1 micromol/L (S/N = 12). Interassay and intraassay coefficients of variation were less than 7% and recovery at three different concentrations was 98.9-102.5%. The LC-MS/MS method for NAA as described involves no extraction and no derivatization, showed no interference and gave excellent recovery with low variability and short analytical time. The method was successfully applied for the retrospective analysis of urine from 21 Canavan disease cases.

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Aspartoacylase Deficiency: The Enzyme Defect in Canavan Disease

Cited by 63 publications

References 5 publications

Viral vectors as tools to model and treat neurodegenerative disorders

Viral vectors as tools to model and treat neurodegenerative disorders

Novel (cys152>arg) missense mutation in an Arab patient with Canavan disease

Stable isotope dilution analysis of N‐acetylaspartic acid in urine by liquid chromatography electrospray ionization tandem mass spectrometry

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