Abnormal epiphyseal development in a feline model of Sandhoff disease.
Abnormal epiphyseal development in a feline model of Sandhoff disease.
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DOI：
10.1002/jor.24803
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Carlson CS
中科院分区：
文献类型：
--
作者：
McNulty MA;Prevatt PB;Nussbaum ER;Randle AN;Johnson AK;Hudson JA;Gray-Edwards HL;Sena-Esteves M;Martin DR;Carlson CS
桑德霍夫病(SD)是由于β-N-乙酰氨基己糖苷酶功能降低，导致神经节苷脂在组织中积聚所致。神经组织主要受到影响，患有婴儿形式的疾病的人通常无法存活超过4岁。目前的治疗方法是解决神经代谢缺陷以延长寿命，然而，这种延长的寿命允许临床疾病在其他组织中变得明显，包括肌肉骨骼系统。SD对骨和关节组织的影响尚未完全确定。在婴儿SD的猫科动物模型中，动物接受了脑内注射腺相关病毒载体的治疗，以向中枢神经系统提供正确水平的氨基己糖苷酶，导致寿命增加两到三倍。随着治疗动物年龄的增长，肌肉骨骼疾病的迹象被识别出来。本研究利用微型计算机断层扫描和组织学研究了受影响猫科动物的骨骼和关节病变。所有受影响的猫都有类似的损伤，无论它们是否接受治疗。SD猫干骺端松质骨显着减少，骨痂大小和形状明显异常。异常的严重程度随着年龄的增长而增加，似乎是由于骨骺软骨内软骨细胞功能的改变，特别是关节-骨盆复合体。年龄较大的猫出现继发性骨关节炎改变。发现的变化类似于粘多糖症患者的变化。临床意义陈述：确定的病变将对因治疗SD的主要神经效应而延长寿命的个人的生活质量产生重大影响。
Sandhoff disease (SD) is caused by decreased function of the enzyme β-N-acetylhexosaminidase, resulting in accumulation of GM2 ganglioside in tissues. Neural tissue is primarily affected and individuals with the infantile form of the disease generally do not survive beyond 4 years of age. Current treatments address neurometabolic deficits to improve lifespan, however, this extended lifespan allows clinical disease to become manifest in other tissues, including the musculoskeletal system. The impact of SD on bone and joint tissues has yet to be fully determined. In a feline model of infantile SD, animals were treated by intracranial injection of adeno-associated virus vectors to supply the central nervous system with corrective levels of hexosaminidase, resulting in a twofold to threefold increase in lifespan. As treated animals aged, signs of musculoskeletal disease were identified. The present study characterized bone and joint lesions from affected cats using micro-computed tomography and histology. All affected cats had similar lesions, whether or not they were treated. SD cats displayed a significant reduction in metaphyseal trabecular bone and markedly abnormal size and shape of epiphyses. Abnormalities increased in severity with age and appear to be due to alteration in the function of chondrocytes within epiphyseal cartilage, particularly the articular-epiphyseal complex. Older cats developed secondary osteoarthritic changes. The changes identified are similar to those seen in humans with mucopolysaccharidoses. Statement of clinical significance: the lesions identified will have significant implications on the quality of life of individuals whose lifespans are extended due to treatments for the primary neurological effects of SD.
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影响因子：
3.7
作者：
Lin, Hsiang-Yu;Shih, Shou-Chuan;Lin, Shuan-Pei
通讯作者：
Lin, Shuan-Pei
影响因子：
3.8
作者：
Tomatsu, Shunji;Almeciga-Diaz, Carlos J.;Montatio, Adriana M.;Yabe, Hiromasa;Tanaka, Akemi;Vu Chi Dung;Giugliani, Roberto;Kubaski, Francyne;Mason, Robert W.;Yasuda, Eriko;Sawamoto, Kazuki;Mackenzie, William;Suzuki, Yasuyuki;Orii, Kenji E.;Barrera, Luis A.;Sly, William S.;Orii, Tadao
通讯作者：
Orii, Tadao
影响因子：
17.1
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
通讯作者：
Martin DR
影响因子：
4.7
作者：
Rockwell HE;McCurdy VJ;Eaton SC;Wilson DU;Johnson AK;Randle AN;Bradbury AM;Gray-Edwards HL;Baker HJ;Hudson JA;Cox NR;Sena-Esteves M;Seyfried TN;Martin DR
通讯作者：
Martin DR
影响因子：
1.9
作者：
Baek, Rena C.;Martin, Douglas R.;Cox, Nancy R.;Seyfried, Thomas N.
通讯作者：
Seyfried, Thomas N.