Research projects

Glucogenosis or glycogen storage diseases (GSD) are a set of infrequent pathologies characterised by an abnormal accumulation of glycogen. Lafora's disease (LD) is glucogenosis with devastating effects, characterised by the early onset of myoclonal epilepsy and the presence of intracellular inclusion bodies composed of abnormal glycogen. LD is caused by the mutation in genes that code for laforine and maline. Laforine/maline has been shown to be involved in the regulation of glycogen accumulation. On the other hand, glycogen accumulation has been described as toxic for neurons.

It has been hypothesized that the excessive accumulation of glycogen causes the dysfunction and/or death of specific cell types, and it is proposed to study whether the activation of mechanisms that limit the accumulation of glycogen represents a feasible therapeutic approach against GSD.

In the first months of this project, in vitro models were established and verified (cultures of neurons and fibroblasts) together with in vivo methods (transgenic mice and flies) based on the gain or loss of function in genes involved in glycogen metabolism. More specifically, embryonic fibroblasts were generated (MEFs) derived from transgenic mice of interest (wild-type, Nhlrc1 KO, Gys1 KO, Gbe1^+/-) and different protocols were defined to trigger the accumulation of glycogen aggregates in these cells. Moreover, transgenic mice and flies have been created and characterised as having an increased accumulation of glycogen in neurons, and it was confirmed that this accumulation is harmful for the organism. Model mice for LD and APBD (adult polyglucosan body disease) are also under study. All these models are highly valuable for the study of molecular targets for the control of this accumulation.