Widespread distribution of transduced brain cells following delivery of AAV vectors into the cerebrospinal fluid (CSF) of the cisterna magna (CM) has been demonstrated in large animal brains. In humans, intraventricular injection is preferred to intracisternal injection for CSF delivery due to the risk of brain stem injury. One study in the dog reported adverse reactions to AAV vectors expressing GFP injected into the lateral ventricle but not when injected into the CM.
View Article and Find Full Text PDFJ Appl Clin Med Phys
November 2024
The Radixact system (Accuray Inc., Sunnyvale, CA) is the latest platform release based on the TomoTherapy technology. The most recent system does not apply a leaf latency model correction after plan optimization to ensure the correct MLC leaf-open time (LOT) agreement between the TPS and machine delivery.
View Article and Find Full Text PDFLysosomal function is impaired in Niemann-Pick disease type C1 (NPC1), a rare and inherited neurodegenerative disorder, resulting in late endosomal/lysosomal accumulation of unesterified cholesterol. The precise pathogenic mechanism of NPC1 remains incompletely understood. In this study, we employed metabolomics to uncover secondary accumulated substances in NPC1.
View Article and Find Full Text PDFAlpha-mannosidosis is caused by a genetic deficiency of lysosomal alpha-mannosidase, leading to the widespread presence of storage lesions in the brain and other tissues. Enzyme replacement therapy is available but is not approved for treating the CNS, since the enzyme does not penetrate the blood-brain barrier. However, intellectual disability is a major manifestation of the disease; thus, a complimentary treatment is needed.
View Article and Find Full Text PDF