Evaluation of neuroretina following i.v. or intra-CSF AAV9 gene replacement in mice with MPS IIIA, a childhood dementia.

Background: Sanfilippo syndrome (mucopolysaccharidosis type IIIA; MPS IIIA) is a childhood dementia caused by inherited mutations in the sulfamidase gene. At present, there is no treatment and children with classical disease generally die in their late teens. Intravenous or intra-cerebrospinal fluid (CSF) injection of AAV9-gene replacement is being examined in human clinical trials; evaluation of the impact on brain disease is an intense focus; however, MPS IIIA patients also experience profound, progressive photoreceptor loss, leading to night blindness.

Repetitive, non-invasive imaging of neurodegeneration, and prevention of it with gene replacement, in mice with Sanfilippo syndrome.

Hampering assessment of treatment outcomes in gene therapy and other clinical trials in patients with childhood dementia is the lack of an objective, non-invasive measure of neurodegeneration. Optical coherence tomography (OCT) is a widely available, rapid, non-invasive, and quantitative method for examining the integrity of the neuroretina. Profound brain and retinal dysfunction occur in patients and animal models of childhood dementia, including Sanfilippo syndrome and we recently revealed a correlation between the age of onset and rate of progression of retinal and brain degeneration in sulfamidase-deficient Sanfilippo mice.

Biomarkers for predicting disease course in Sanfilippo syndrome: An urgent unmet need in childhood-onset dementia.

Sanfilippo syndrome (MPS III) is an autosomal recessive inherited disorder causing dementia in children, following an essentially normal early developmental period. First symptoms typically include delayed language development, hyperactivity and/or insomnia from 2 years of age, followed by unremitting and overt loss of previously acquired skills. There are no approved treatments, and the median age of death is 18 years.

A Delayed Presentation of Bilateral Adrenal Hemorrhage Secondary to COVID-19.

Background/objective: Bilateral adrenal hemorrhage is a rare cause of adrenal insufficiency. Cases have been reported of acute adrenal crisis with bilateral adrenal hemorrhage during acute coronavirus disease of 2019 (COVID-19). Our objective was to report a delayed presentation of acute adrenal crisis with bilateral adrenal hemorrhage 2 months after COVID-19.

The ovine Type II Gaucher disease model recapitulates aspects of human brain disease.

Acute neuronopathic (type II) Gaucher disease (GD) is a devastating, untreatable neurological disorder resulting from mutations in the glucocerebrosidase gene (GBA1), with subsequent accumulation of glucosylceramide and glucosylsphingosine. Patients experience progressive decline in neurological function, with onset typically within the first three-to-six months of life and premature death before two years. Mice and drosophila with GD have been described, however little is known about the brain pathology observed in the naturally occurring ovine model of GD.