Ketogenic diet reduces Lafora bodies in murine Lafora disease

Lafora disease (LD) is a teenage-onset fatal progressive myoclonus epilepsy caused by loss-of-function mutations in the EPM2A gene encoding the glycogen phosphatase laforin or EPM2B encoding the laforin-interacting ubiquitin E3 ligase malin. Concerted actions of glycogen synthase (GS) and branching enzyme generate normal short-branched soluble glycogen. In LD, some glycogen molecules develop long branches, precipitate, and accumulate into pathognomonic and pathogenic Lafora bodies (LBs). The precise mechanism by which the laforin-malin complex mitigates this is unknown, but thought to involve GS downregulation. In fact, transgenic GS downregulation in LD mouse models reduces LB formation and rescues the disease.1,2