A therapeutic approach for polyglucosan or glycogen overload diseases

Adult polyglucosan inclusion disease (APBD) and Lafora’s disease are two neurological diseases with an overload of abnormal glycogen (polyglucosan).

In the absence of a branching enzyme, as in APBD, glycogen does not branch and elongation of the glycogen chain by glycogen synthase results in the accumulation of insoluble polyglucosan.

  • By inhibiting the expression of the glycogen synthase gene, Gys1, or the enzymes that activate it, American researchers have achieved the reduction or absence of polyglucosan inclusions and the correction of neuropathological lesions in mouse models of APBD or Lafora disease.
  • The administration of an artificial microRNA (ami-RNA) targeting Gys1 using AAV9 to a mouse model significantly reduces polyglucosan inclusions and signs of inflammation of the nervous tissue.

The authors conclude that this type of treatment could benefit other polyglucosan or normal glycogen overload diseases, such as Pompe disease.


AAV-Mediated Artificial miRNA Reduces Pathogenic Polyglucosan Bodies and Neuroinflammation in Adult Polyglucosan Body and Lafora Disease Mouse Models. Gumusgoz E, Kasiri S, Guisso DR, Wu J, Dear M, Verhalen B, Minassian BA. Neurotherapeutics. 2022 Mar 28.