Inhibiting glycogen synthesis prevents Lafora disease in a mouse model

Ann Neurol. 2013 Aug;74(2):297-300. doi: 10.1002/ana.23899.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dual-Specificity Phosphatases / genetics
  • Gene Knockout Techniques
  • Glycogen / antagonists & inhibitors*
  • Glycogen / biosynthesis*
  • Glycogen Synthase / genetics
  • Glycogen Synthase / metabolism
  • Lafora Disease / pathology
  • Lafora Disease / physiopathology
  • Lafora Disease / prevention & control*
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Tyrosine Phosphatases, Non-Receptor


  • Glycogen
  • Glycogen Synthase
  • Dual-Specificity Phosphatases
  • Epm2a protein, mouse
  • Protein Tyrosine Phosphatases, Non-Receptor