Igdoura S A, Mertineit C, Trasler J M, Gravel R A
Montreal Children's Hospital Research Institute and Department of Human Genetics, McGill University, Quebec, Canada.
Hum Mol Genet. 1999 Jun;8(6):1111-6. doi: 10.1093/hmg/8.6.1111.
Tay-Sachs disease is a severe, inherited disease of the nervous system caused by accumulation of the brain lipid GM2 ganglioside. Mouse models of Tay-Sachs disease have revealed a metabolic bypass of the genetic defect based on the more potent activity of the enzyme sialidase towards GM2. To determine whether increasing the level of sialidase would produce a similar effect in human Tay-Sachs cells, we introduced a human sialidase cDNA into neuroglia cells derived from a Tay-Sachs fetus and demonstrated a dramatic reduction in the accumulated GM2. This outcome confirmed the reversibility of GM2 accumulation and opens the way to pharmacological induction or activation of sialidase for the treatment of human Tay-Sachs disease.
泰-萨克斯病是一种严重的遗传性神经系统疾病，由大脑脂质GM2神经节苷脂的积累引起。泰-萨克斯病的小鼠模型显示，基于唾液酸酶对GM2更强的活性，存在一种绕过基因缺陷的代谢途径。为了确定提高唾液酸酶水平是否会在人类泰-萨克斯细胞中产生类似的效果，我们将人类唾液酸酶cDNA导入来自泰-萨克斯病胎儿的神经胶质细胞，并证明积累的GM2显著减少。这一结果证实了GM2积累的可逆性，并为通过药理学方法诱导或激活唾液酸酶来治疗人类泰-萨克斯病开辟了道路。
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