Buchet Delphine, Serguera Ché, Zennou Véronique, Charneau Pierre, Mallet Jacques
Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, Bat. CERVI, Hôpital de la Pitié-Salpêtrière, 83, Boulevard de l'Hôpital, 75013 Paris, France.
Mol Cell Neurosci. 2002 Mar;19(3):389-401. doi: 10.1006/mcne.2001.1086.
Mucopolysaccharidosis type VII (MPS VII) is an inherited disease caused by beta-glucuronidase (beta-glu) deficiency. This deficiency results in the lysosomal accumulation of glycosaminoglycans in all tissues and affects a wide range of organs, including the central nervous system (CNS). Gene transfer is a promising approach to therapy for MPS VII because it allows extensive delivery of the enzyme to the affected tissues. We studied neurotransplantation of primary human cells to supply beta-glucuronidase to the CNS. Human neural progenitor cells (HNPC) were amplified and cotransduced with two lentiviral vectors, one encoding the green fluorescent protein and the other the human beta-glu. We show that these cells strongly expressed both transgenes in culture. When grafted into the mouse striatum, HNPC differentiated into neurons and astrocytes and expressed the two transgenes for at least 6 months. This study therefore paves the way for the treatment of MPS VII by long-term delivery of the appropriate enzyme.
黏多糖贮积症VII型（MPS VII）是一种由β-葡萄糖醛酸酶（β-glu）缺乏引起的遗传性疾病。这种缺乏导致糖胺聚糖在所有组织的溶酶体中积累，并影响包括中枢神经系统（CNS）在内的广泛器官。基因转移是治疗MPS VII的一种有前景的方法，因为它能将该酶广泛递送至受影响的组织。我们研究了原代人类细胞的神经移植，以向中枢神经系统提供β-葡萄糖醛酸酶。人类神经祖细胞（HNPC）被扩增，并与两种慢病毒载体共转导，一种编码绿色荧光蛋白，另一种编码人类β-glu。我们表明，这些细胞在培养中强烈表达两种转基因。当移植到小鼠纹状体中时，HNPC分化为神经元和星形胶质细胞，并至少6个月表达这两种转基因。因此，这项研究为通过长期递送适当的酶来治疗MPS VII铺平了道路。
