Indiana University School of Medicine-Muncie, Ball State University, Muncie, IN.
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.
拉佛拉病（LD）是一种致命的进行性肌阵挛性癫痫，其神经病理学特征为异常结构的糖原和蛋白质（拉佛拉体[LBs]）聚集和神经退行性变。糖原合成是否可以通过抑制糖原合成来预防，以及它们是否具有致病性仍不确定。我们在 LD 小鼠中遗传消除了大脑中的糖原合成。这导致 LB 形成、神经退行性变和癫痫易感性的长期预防。这项研究确立了糖原合成是 LB 形成所必需的，并且 LB 是致病性的。它为使用已知和未来的糖原合成小分子抑制剂治疗 LD 开辟了一个治疗窗口。
