Gene Therapy in Animal Models of the Gangliosidoses: From Presentation to Human Clinical TrialsHeather L. Gray-Edwards

摘要

GMl and GM2 gangliosidosis (Tay-Sachs, Sandhoff disease, GM2 activator protein deficiency) are monogenetic diseases that result from deficiencies of p-galactosidase (P-gal), hexosaminidase (Hex), or GM2 activator protein, which are enzymes of the ganglioside degradation pathway. These are global diseases resulting in ganglioside buildup in all tissues, but have primary neurodegenerative presentation due to the inherent concentration of gangliosides within neurons. These diseases are clinically indistinguishable in humans and symptoms present in children with lack or loss of developmental milestones (sitting, crawling, etc.) and progress to inability to swallow, seizures and eventual semi-vegetative state. As with most human diseases, these diseasesare also naturally occurring in animals (cats and sheep), and are maintained for study and testing of novel therapeutics.