Ppp1r3d deficiency preferentially inhibits neuronal and cardiac Lafora body formation in a mouse model of the fatal epilepsy Lafora disease

2020 ◽  
Author(s):  
Lori Israelian ◽  
Silvia Nitschke ◽  
Peixiang Wang ◽  
Xiaochu Zhao ◽  
Ami M. Perri ◽  
...  
Keyword(s):  
Mouse Model ◽  
Lafora Disease ◽  
Body Formation ◽  
Lafora Body

scholarly journals Gys1 antisense therapy rescues neuropathological bases of murine Lafora disease

2021 ◽  
Author(s):  
Saija Ahonen ◽  
Silvia Nitschke ◽  
Tamar R. Grossman ◽  
Holly Kordasiewicz ◽  
Peixiang Wang ◽  
...  
Keyword(s):  
Antisense Oligonucleotide ◽  
Glycogen Synthase ◽  
Lafora Disease ◽  
Neuroinflammatory Response ◽  
Glycogen Accumulation ◽  
Body Formation ◽  
Lafora Bodies ◽  
Progressive Myoclonus Epilepsy ◽  
Myoclonus Epilepsy ◽  
Lafora Body

AbstractLafora disease is a fatal progressive myoclonus epilepsy. At root, it is due to constant acquisition of branches that are too long in a subgroup of glycogen molecules, leading them to precipitate and accumulate into Lafora bodies, which drive a neuroinflammatory response and neurodegeneration. As a potential therapy, we aimed to downregulate glycogen synthase, the enzyme responsible for glycogen branch elongation, in the disease’s mouse models. We synthesized an antisense oligonucleotide (Gys1-ASO) that targets the mRNA of the brain-expressed glycogen synthase 1 gene (Gys1). We administered Gys1-ASO by intracerebroventricular injection and analyzed the pathological hallmarks of Lafora disease, namely glycogen accumulation, Lafora body formation, and neuroinflammation. Gys1-ASO prevented Lafora body formation in young mice that had not yet formed them. In older mice that already exhibited Lafora bodies, Gys1-ASO inhibited further accumulation, markedly preventing large Lafora bodies characteristic of advanced disease. Inhibition of Lafora body formation was associated with prevention of astrogliosis and strong trends towards correction of dysregulated expression of disease immune and neuroinflammatory markers. Lafora disease manifests gradually in previously healthy teenagers. Our work provides proof of principle that an antisense oligonucleotide targeting the GYS1 mRNA could prevent, and halt progression of, this catastrophic epilepsy.

scholarly journals Increased Laforin and Laforin Binding to Glycogen Underlie Lafora Body Formation in Malin-deficient Lafora Disease

2012 ◽  
Vol 287 (30) ◽  
pp. 25650-25659 ◽  
Author(s):  
Erica Tiberia ◽  
Julie Turnbull ◽  
Tony Wang ◽  
Alessandra Ruggieri ◽  
Xiao-Chu Zhao ◽  
...  
Keyword(s):  
Lafora Disease ◽  
Body Formation ◽  
Lafora Body

scholarly journals Everolimus does not prevent Lafora body formation in murine Lafora disease

2017 ◽  
Vol 3 (1) ◽  
pp. e127 ◽  
Author(s):  
Navin Mishra ◽  
Peixiang Wang ◽  
Danielle Goldsmith ◽  
Xiaochu Zhao ◽  
Yunlin Xue ◽  
...  
Keyword(s):  
Lafora Disease ◽  
Body Formation ◽  
Lafora Body

scholarly journals Inhibiting glycogen synthesis prevents lafora disease in a mouse model

2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Bartholomew A Pederson ◽  
Julie Turnbull ◽  
Jonathan R Epp ◽  
Staci A Weaver ◽  
Xiaochu Zhao ◽  
...  
Keyword(s):  
Mouse Model ◽  
Glycogen Synthesis ◽  
Lafora Disease

scholarly journals Progressive Myoclonic Epilepsy: Review Article with A Case Report of Lafora Disease

2018 ◽  
Vol 42 (3) ◽  
pp. 138-147
Author(s):  
Selina Husna Banu ◽  
Mashaya Zaman Koli
Keyword(s):  
Autosomal Recessive ◽  
Early Stage ◽  
Clinical History ◽  
Genetic Mutation ◽  
Myoclonic Epilepsy ◽  
Epilepsy Syndrome ◽  
Lafora Disease ◽  
Clinical Criteria ◽  
Lafora Body ◽  
Progressive Myoclonic Epilepsy

Progressive myoclonic epilepsy (PME) is an autosomal recessive, apparently a rare complex epilepsy syndrome. Among different types of PME, lafora body disease is more quickly progressive usually fatal within 2nd and 3rd decade. They are characterized by childhood or adolescent onset difficult to control multiple type seizures including myoclonous, generalized tonic clonic, absences, psychomotor regression with ataxia, dementia, dysarthria, visual hallucinations, and other general features. Early suspicion is important that leads to the rational diagnostic workout. The electro-clinical criteria would help a lot to exclude the benign epilepsy syndrome such as juvenile myoclonic epilepsy (JME) and suspect PME at the early stage of the complex epilepsy syndrome. Diagnosis is further clarified and confirmed by finding lafora body in skin and genetic study. Genetic mutation found in more than 87% cases in EPM2A gene or the EPM2B also known as NHLRC1 gene and are inherited in an autosomal recessive manner. EMP2A gene is located on chromosome 6q24. They are reported from Mediterranean basin, central Asia, India, Pakistan, northern Africa and Middle East where consanguineous marriage is common. We report a diagnosed case for the first time in Bangladesh. With the detail clinical history, rational use of the available investigation tools and clinical suspicion, diagnosis of the disorder at its early stage is possible. The rapid progress in genetic therapy would be a great hope in near future. Bangladesh J Child Health 2018; VOL 42 (3) :138-147

scholarly journals In vivo glutamate clearance defects in a mouse model of Lafora disease

2019 ◽  
Vol 320 ◽  
pp. 112959 ◽  
Author(s):  
C. Muñoz-Ballester ◽  
N. Santana ◽  
E. Perez-Jimenez ◽  
R. Viana ◽  
F. Artigas ◽  
...  
Keyword(s):  
Mouse Model ◽  
Lafora Disease

scholarly journals Pharmacological Interventions to Ameliorate Neuropathological Symptoms in a Mouse Model of Lafora Disease

2015 ◽  
Vol 53 (2) ◽  
pp. 1296-1309 ◽  
Author(s):  
Arnaud Berthier ◽  
Miguel Payá ◽  
Ana M. García-Cabrero ◽  
Maria Inmaculada Ballester ◽  
Miguel Heredia ◽  
...  
Keyword(s):  
Mouse Model ◽  
Lafora Disease ◽  
Pharmacological Interventions

Transcriptional profiling of a mouse model for Lafora disease reveals dysregulation of genes involved in the expression and modification of proteins

2005 ◽  
Vol 387 (2) ◽  
pp. 62-67 ◽  
Author(s):  
Subramaniam Ganesh ◽  
Naomi Tsurutani ◽  
Kenji Amano ◽  
Shuchi Mittal ◽  
Chiharu Uchikawa ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transcriptional Profiling ◽  
Lafora Disease

scholarly journals Glycogen metabolism in tissues from a mouse model of Lafora disease

2007 ◽  
Vol 457 (2) ◽  
pp. 264-269 ◽  
Author(s):  
Wei Wang ◽  
Hannes Lohi ◽  
Alexander V. Skurat ◽  
Anna A. DePaoli-Roach ◽  
Berge A. Minassian ◽  
...  
Keyword(s):  
Mouse Model ◽  
Glycogen Metabolism ◽  
Lafora Disease
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