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Inhibiting glycogen synthesis prevents lafora disease in a mouse model
Author(s) -
Pederson Bartholomew A.,
Turnbull Julie,
Epp Jonathan R.,
Weaver Staci A.,
Zhao Xiaochu,
Pencea Nela,
Roach Peter J.,
Frankland Paul W.,
Ackerley Cameron A.,
Minassian Berge A.
Publication year - 2013
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.23899
Subject(s) - lafora disease , neurodegeneration , glycogen , progressive myoclonus epilepsy , epilepsy , glycogen synthase , neuroscience , biology , chemistry , biochemistry , disease , medicine , enzyme , phosphatase
Lafora disease (LD) is a fatal progressive myoclonus epilepsy characterized neuropathologically by aggregates of abnormally structured glycogen and proteins (Lafora bodies [LBs]), and neurodegeneration. Whether LBs could be prevented by inhibiting glycogen synthesis and whether they are pathogenic remain uncertain. We genetically eliminated brain glycogen synthesis in LD mice. This resulted in long‐term prevention of LB formation, neurodegeneration, and seizure susceptibility. This study establishes that glycogen synthesis is requisite for LB formation and that LBs are pathogenic. It opens a therapeutic window for potential treatments in LD with known and future small molecule inhibitors of glycogen synthesis. Ann Neurol 2013;74:297–300