Long-term progression of retinal degeneration in a preclinical model of CLN7 Batten disease as a baseline for testing clinical therapeutics.
Long-term progression of retinal degeneration in a preclinical model of CLN7 Batten disease as a baseline for testing clinical therapeutics.
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DOI：
10.1016/j.ebiom.2022.104314
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发表时间：
2022-11
期刊：
影响因子：
11.1
通讯作者：
Wert, Katherine J.
中科院分区：
文献类型：
--
作者：
Rowe, Ashley A.;Chen, Xin;Nettesheim, Emily R.;Issioui, Yacine;Dong, Thomas;Hu, Yuhui;Messahel, Souad;Kayani, Saima N.;Gray, Steven J.;Wert, Katherine J.
关键词：
巴顿病的特点是认知和运动障碍，视网膜变性和癫痫发作导致过早死亡。最近的研究显示了CLN7巴滕病的基因治疗方法的有效性。这种基因治疗方法有望治疗认知和运动障碍，但不太可能延缓视力丧失。此外，CLN7 Batten病患者视网膜变性的自然进展尚不清楚。我们对5例患有CLN7巴滕病的患者进行了目视检查，发现患者在生命的前5年内退行性变进展严重。为了更好地了解疾病进展，我们对CLN7 Batten病的临床前小鼠模型的视网膜进行了表征，通过小鼠出现瘫痪和过早死亡的年龄。我们发现这个临床前模型早期显示双极突触缺陷的光感受器的迹象，并显示杆-锥营养不良和双极细胞的晚期损失。这种视力丧失不仅可以通过组织学来追踪，还可以使用类似于人类患者的临床实时成像。罕见的小儿神经退行性疾病的自然史研究因其快速退行性和患者的有限可用性而变得复杂。在临床前模型中变性的表征允许未来的实验更好地了解视网膜疾病进展的机制，以便找到治疗患者的治疗方法，以及评估这些治疗方案用于未来的人体临床试验。P30EY030413和5T32GM131945-03。
Batten disease is characterized by cognitive and motor impairment, retinal degeneration, and seizures leading to premature death. Recent studies have shown efficacy for a gene therapy approach for CLN7 Batten disease. This gene therapy approach is promising to treat cognitive and motor impairment, but is not likely to delay vision loss. Additionally, the natural progression of retinal degeneration in CLN7 Batten disease patients is not well-known. We performed visual examinations on five patients with CLN7 Batten disease and found that patients were far progressed in degeneration within their first five years of life. To better understand the disease progression, we characterized the retina of a preclinical mouse model of CLN7 Batten disease, through the age at which mice present with paralysis and premature death. We found that this preclinical model shows signs of photoreceptor to bipolar synaptic defects early, and displays rod-cone dystrophy with late loss of bipolar cells. This vision loss could be followed not only via histology, but using clinical live imaging similar to that used in human patients. Natural history studies of rare paediatric neurodegenerative conditions are complicated by the rapid degeneration and limited availability of patients. Characterization of degeneration in the preclinical model allows for future experiments to better understand the mechanisms underlying the retinal disease progression in order to find therapeutics to treat patients, as well as to evaluate these therapeutic options for future human clinical trials. , P30EY030413, and 5T32GM131945-03.
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DOI：
10.1016/j.bbadis.2015.05.011
发表时间：
2015-10
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Mole SE;Cotman SL
通讯作者：
Cotman SL
影响因子：
16.6
作者：
Lopez-Fabuel I;Garcia-Macia M;Buondelmonte C;Burmistrova O;Bonora N;Alonso-Batan P;Morant-Ferrando B;Vicente-Gutierrez C;Jimenez-Blasco D;Quintana-Cabrera R;Fernandez E;Llop J;Ramos-Cabrer P;Sharaireh A;Guevara-Ferrer M;Fitzpatrick L;Thompton CD;McKay TR;Storch S;Medina DL;Mole SE;Fedichev PO;Almeida A;Bolaños JP
通讯作者：
Bolaños JP
影响因子：
3.5
作者：
Brandenstein, Laura;Schweizer, Michaela;Storch, Stephan
通讯作者：
Storch, Stephan
影响因子：
12.4
作者：
Holthaus, Sophia-Martha Kleine;Ribeiro, Joana;Ali, Robin R.
通讯作者：
Ali, Robin R.
影响因子：
6
作者：
Kohlschuetter, Alfried;Schulz, Angela;Storch, Stephan
通讯作者：
Storch, Stephan