Natural history of Tay-Sachs disease in sheep.
Natural history of Tay-Sachs disease in sheep.
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绵羊泰-萨二氏病的自然史
DOI：
10.1016/j.ymgme.2021.08.009
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发表时间：
2021-09
影响因子：
3.8
通讯作者：
Gray-Edwards H
中科院分区：
文献类型：
--
作者：
Story B;Taghian T;Gallagher J;Koehler J;Taylor A;Randle A;Nielsen K;Gross A;Maguire A;Carl S;Johnson S;Fernau D;Diffie E;Cuddon P;Corado C;Chandra S;Sena-Esteves M;Kolodny E;Jiang X;Martin D;Gray-Edwards H
泰萨克斯病 (TSD) 是一种致命的神经退行性疾病，由 β-N-乙酰己糖胺酶 A (HexA) 缺乏引起。 TSD 自然发生在雅各布羊身上，是唯一的 TSD 实验模型。绵羊 TSD 再现了与青少年发病和晚发 TSD 患者相似的神经系统特征。由于关于 TSD 病理学的人类文献很少，因此需要更好地了解绵羊 TSD 大脑的自然历史（其与儿童的大脑处于同一数量级），以评估治疗和描述发生的病理事件。为了让临床医生和研究人员更清楚地了解患者的纵向病理学，我们比较了轻度症状（3 个月）、中度症状（6 个月）或严重受影响的 TSD 绵羊（人道终点在约 9 月龄）的临床症状和脑部病理学。 TSD 绵羊脑脊液中 GM2 神经节苷脂的增加以及 MRS 上 TSD 特异性生物标志物（牛磺酸）与疾病严重程度相关。在 TSD 绵羊的组织病理学上观察到小胶质细胞活化和反应性星形胶质细胞，少突胶质细胞密度普遍降低。髓鞘形成减少主要发生在前脑，MRI 上显示白质损失。 GM2和GM3神经节苷脂增加并且在各组织中分布不同。绵羊模型中 TSD 的研究提供了自然史，有助于阐明 TSD 的病理生理学，这对于在人类患者中评估新疗法至关重要。
Tay-Sachs disease (TSD) is a fatal neurodegenerative disease caused by a deficiency of the enzyme β-N-acetylhexosaminidase A (HexA). TSD naturally occurs in Jacob sheep is the only experimental model of TSD. TSD in sheep recapitulates neurologic features similar to juvenile onset and late onset TSD patients. Due to the paucity of human literature on pathology of TSD, a better natural history in the sheep TSD brain, which is on the same order of magnitude as a child’s, is necessary for evaluating therapy and characterizing the pathological events that occur. To provide clinicians and researchers with a clearer understanding of longitudinal pathology in patients, we compare spectrum of clinical signs and brain pathology in mildly symptomatic (3-months), moderately symptomatic (6-months), or severely affected TSD sheep (humane endpoint at ~9-months of age). Increased GM2 ganglioside in the CSF of TSD sheep and a TSD specific biomarker on MRS (taurine) correlate with disease severity. Microglial activation and reactive astrocytes were observed globally on histopathology in TSD sheep with a widespread reduction in oligodendrocyte density. Myelination is reduced primarily in the forebrain illustrated by loss of white matter on MRI. GM2 and GM3 ganglioside were increased and distributed differently in various tissues. The study of TSD in the sheep model provides a natural history to shed light on the pathophysiology of TSD, which is of utmost importance due to novel therapeutics being assessed in human patients.
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影响因子：
12.4
作者：
Gray-Edwards, Heather L.;Regier, Debra S.;Martin, Douglas R.
通讯作者：
Martin, Douglas R.
影响因子：
11
作者：
Delnooz, C. C. S.;Lefeber, D. J.;van de Warrenburg, B. P. C.
通讯作者：
van de Warrenburg, B. P. C.
影响因子：
3.8
作者：
Gray-Edwards, Heather L.;Brunson, Brandon L.;Martin, Douglas R.
通讯作者：
Martin, Douglas R.
影响因子：
1.4
作者：
Imamura, A.;Miyajima, H.;Oril, K. O.
通讯作者：
Oril, K. O.
猫Sandhoff疾病中疾病进展和AAV治疗功效的生物标志物。
影响因子：
5.3
作者：
Bradbury, Allison M.;Gray-Edwards, Heather L.;Shirley, Jamie L.;McCurdy, Victoria J.;Colaco, Alexandria N.;Randle, Ashley N.;Christopherson, Pete W.;Bird, Allison C.;Johnson, Aime K.;Wilson, Diane U.;Hudson, Judith A.;De Pompa, Nicholas L.;Sorjonen, Donald C.;Brunson, Brandon L.;Jeyakumar, Mylvaganam;Platt, Frances M.;Baker, Henry J.;Cox, Nancy R.;Sena-Esteves, Miguel;Martin, Douglas R.
通讯作者：
Martin, Douglas R.