News Finding: "The continuous supply of enzyme produced by the genome-edited liver cells in these young mice not only protected organs and tissue from damage, but importantly also promoted passage across the blood brain barrier to exert neuroprotective effects.
Paper Finding: Remarkably, the high level of IDS expression achieved in animals administered the highest dose of ZFN+hIDS donor encoding vectors prevented emergence of a neurocognitive deficit exhibited in control MPS II animals.
News Context: Importantly, treatment with Sangamo's genome editing therapy at the highest dose level also prevented the development of neurocognitive deficit in the young MPS II model mice, as measured by the Barnes Maze test. "The continuous supply of enzyme produced by the genome-edited liver cells in these young mice not only protected organs and tissue from damage, but importantly also promoted passage across the blood brain barrier to exert neuroprotective effects. The absence of IDS enzyme, results in lysosomal GAG accumulation, leading to skeletal abnormalities, cardiac and respiratory obstructions, organomegaly, and in severe cases of the disease neurological impairment and death when patients reach adolescence.
Paper Context: The levels of hIDS achieved in the circulation increased in a dose-dependent manner, and IDS was subsequently taken up from the circulation by secondary tissues, resulting in normalization of GAG storage levels. Remarkably, the high level of IDS expression achieved in animals administered the highest dose of ZFN+hIDS donor encoding vectors prevented emergence of a neurocognitive deficit exhibited in control MPS II animals. 14, However, episomal expression of a transgene in the liver is unlikely to achieve long-term expression in a pediatric patient population, due to the high proliferative rate of hepatocytes in this population.