Sustained normalization of neurological disease after intracranial gene therapy in a feline model.
Sustained normalization of neurological disease after intracranial gene therapy in a feline model.
复制标题
DOI：
10.1126/scitranslmed.3007733
复制
发表时间：
2014-04-09
影响因子：
17.1
通讯作者：
Martin DR
中科院分区：
文献类型：
--
作者：
McCurdy VJ;Johnson AK;Gray-Edwards HL;Randle AN;Brunson BL;Morrison NE;Salibi N;Johnson JA;Hwang M;Beyers RJ;Leroy SG;Maitland S;Denney TS;Cox NR;Baker HJ;Sena-Esteves M;Martin DR
进行性衰弱的神经缺陷是猫GM1神经节苷脂沉积症的特征，这是一种由溶酶体β -半乳糖苷酶缺乏引起的溶酶体贮积症。对于患病儿童没有有效的治疗方法，他们往往在5岁前死亡。在当前的研究中，一种携带治疗基因的腺相关病毒载体被双侧注射到GM1神经节苷脂沉积症猫模型的两个脑靶点（丘脑和小脑深部核团）中。基因治疗使整个大脑和脊髓的β -半乳糖苷酶活性和贮积物恢复正常。12只接受治疗的GM1动物的平均存活时间>38个月，而未接受治疗的动物为8个月。8只存活的接受治疗的动物中有7只疾病恢复正常，许多症状包括步态缺陷和姿势失衡都消失了。在大型动物模型中通过基因治疗对有限的颅内靶点进行治疗后，GM1神经节苷脂沉积症疾病表型得到持续纠正，这表明这种方法可能对治疗人类这种溶酶体贮积症有用。
Progressive debilitating neurological defects characterize feline GM1 gangliosidosis, a lysosomal storage disease caused by deficiency of lysosomal β-galactosidase. No effective therapy exists for affected children, who often die before age 5. In the current study, an adeno-associated viral vector carrying the therapeutic gene was injected bilaterally into two brain targets (thalamus and deep cerebellar nuclei) of a feline model of GM1 gangliosidosis. Gene therapy normalized β-galactosidase activity and storage throughout the brain and spinal cord. The mean survival of 12 treated GM1 animals was >38 months compared to 8 months for untreated animals. Seven of the 8 treated animals remaining alive demonstrated normalization of disease, with abrogation of many symptoms including gait deficits and postural imbalance. Sustained correction of the GM1 gangliosidosis disease phenotype after limited intracranial targeting by gene therapy in a large animal model suggests that this approach may be useful for treating the human version of this lysosomal storage disorder.
登录
查看更多内容
影响因子：
12.4
作者：
Arruda, VR;Fields, PA;High, KA
通讯作者：
High, KA
影响因子：
3.5
作者：
De Grandis, E.;Di Rocco, M.;Rossi, A.
通讯作者：
Rossi, A.
DOI：
10.1089/gte.2005.9.126
发表时间：
2005-06-01
期刊：
GENETIC TESTING
影响因子：
--
作者：
Georgiou, T;Stylianidou, G;Drousiotou, A
通讯作者：
Drousiotou, A
影响因子：
6
作者：
Jaski, Brian E.;Jessup, Mariell L.;Mancini, Donna M.;Cappola, Thomas P.;Pauly, Daniel F.;Greenberg, Barry;Borow, Kenneth;Dittrich, Howard;Zsebo, Krisztina M.;Hajjar, Roger J.
通讯作者：
Hajjar, Roger J.
DOI：
10.1155/2012/751510
发表时间：
2012
期刊：
Epilepsy research and treatment
影响因子：
--
作者：
Blair RD
通讯作者：
Blair RD