Making the White Matter Matters: Progress in Understanding Canavan’s Disease and Therapeutic Interventions Through Eight Decades

Ahmed, Seemin Seher; Gao, Guangping

doi:10.1007/8904_2014_356

Cited by 6 publications

(1 citation statement)

References 92 publications

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“…The pathognomonic biochemical marker for CD is NAA accumulation in blood, urine, CSF and amniotic fluid. The role of NAA accumulation in the pathogenesis of progressive myelin degeneration in CD has been the subject of multiple investigations and theories [17,18] well summarized by several authors [19]. NAA and particularly ASPA are believed to play a role in the molecular efflux water pump system to the extracellular fluid, obeying to a transport gradient between two juxtaposed anabolic (neurons) and catabolic (oligodendrocytes) compartments.…”

Section: Discussionmentioning

confidence: 99%

Canavan’s spongiform leukodystrophy (Aspartoacylase deficiency) with emphasis on sonographic features in infancy: description of a case report and review of the literature

et al. 2022

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Canavan disease (CD; MIM 271,900) or spongy degeneration of the central nervous system (CNS) is a lethal, rare autosomal recessive leukodystrophy, first described in 1931 (Canavan in Arch Neurol Psychiatry 25: 299–308, 1931). The clinical presentation includes severe neurologic impairment and macrocephaly with onset of symptoms at the age of 3–5 months. Biochemical and genetic fundamentals of the disease are elucidated. Imaging diagnosis is principally based on MRI with important role of MR spectroscopy. We report the cerebral sonographic findings in a severely affected infant with CD: Diffuse hyperechogenicity and small multicystic changes of white matter as well as an inverted pattern of echogenicity between cortical gray and subcortical white matter. These findings are compared to to the few cases found in literature and to normal ultrasound examples. Finally, ultrasound and MRI imaging findings are correlated.

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Section: Discussionmentioning

confidence: 99%

Canavan’s spongiform leukodystrophy (Aspartoacylase deficiency) with emphasis on sonographic features in infancy: description of a case report and review of the literature

et al. 2022

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Cell‐Based Therapy for Canavan Disease Using Human iPSC‐Derived NPCs and OPCs

et al. 2020

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Canavan disease (CD) is a fatal leukodystrophy caused by mutation of the aspartoacylase (ASPA) gene, which leads to deficiency in ASPA activity, accumulation of the substrate N-acetyl-L-aspartate (NAA), demyelination, and spongy degeneration of the brain. There is neither a cure nor a standard treatment for this disease. In this study, human induced pluripotent stem cell (iPSC)-based cell therapy is developed for CD. A functional ASPA gene is introduced into patient iPSC-derived neural progenitor cells (iNPCs) or oligodendrocyte progenitor cells (iOPCs) via lentiviral transduction or TALEN-mediated genetic engineering to generate ASPA iNPC or ASPA iOPC. After stereotactic transplantation into a CD (Nur7) mouse model, the engrafted cells are able to rescue major pathological features of CD, including deficient ASPA activity, elevated NAA levels, extensive vacuolation, defective myelination, and motor function deficits, in a robust and sustainable manner. Moreover, the transplanted mice exhibit much prolonged survival. These genetically engineered patient iPSC-derived cellular products are promising cell therapies for CD. This study has the potential to bring effective cell therapies, for the first time, to Canavan disease children who have no treatment options. The approach established in this study can also benefit many other children who have deadly genetic diseases that have no cure.

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Control of seizures by ketogenic diet-induced modulation of metabolic pathways

Clanton

Akabani

et al. 2016

Amino Acids

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Epilepsy is too complex to be considered as a disease; it is more of a syndrome, characterized by seizures, which can be caused by a diverse array of afflictions. As such, drug interventions that target a single biological pathway will only help the specific individuals where that drug's mechanism of action is relevant to their disorder. Most likely, this will not alleviate all forms of epilepsy nor the potential biological pathways causing the seizures, such as glucose/amino acid transport, mitochondrial dysfunction, or neuronal myelination. Considering our current inability to test every individual effectively for the true causes of their epilepsy and the alarming number of misdiagnoses observed, we propose the use of the ketogenic diet (KD) as an effective and efficient preliminary/long-term treatment. The KD mimics fasting by altering substrate metabolism from carbohydrates to fatty acids and ketone bodies (KBs). Here, we underscore the need to understand the underlying cellular mechanisms governing the KD's modulation of various forms of epilepsy and how a diverse array of metabolites including soluble fibers, specific fatty acids, and functional amino acids (e.g., leucine, D-serine, glycine, arginine metabolites, and N-acetyl-cysteine) may potentially enhance the KD's ability to treat and reverse, not mask, these neurological disorders that lead to epilepsy.

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Making the White Matter Matters: Progress in Understanding Canavan’s Disease and Therapeutic Interventions Through Eight Decades

Cited by 6 publications

References 92 publications

Canavan’s spongiform leukodystrophy (Aspartoacylase deficiency) with emphasis on sonographic features in infancy: description of a case report and review of the literature

Canavan’s spongiform leukodystrophy (Aspartoacylase deficiency) with emphasis on sonographic features in infancy: description of a case report and review of the literature

Cell‐Based Therapy for Canavan Disease Using Human iPSC‐Derived NPCs and OPCs

Control of seizures by ketogenic diet-induced modulation of metabolic pathways

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