Research projects

Several congenital muscular dystrophies (CMD) are in fact glycosylation disorders. Several genes involved in the Walker-Warburg syndrome (WWS) and other CMDs have been identified, all of them cause hypoglycosylation of α-Distroglican (α-DG). Of these genes, only the functions of POMT1 and POMT2, which are responsible for catalysis of the first stage of synthesis of O-mannosylglycans in the endoplasmic reticulum, have been elucidated.

No specific treatment exists for any CMD, and palliative care is essential to preserve the functional capacity of affected individuals, to increase their life expectancy. However, recent studies indicate that a potential effective therapy would be the stimulation of glycosylation in the affected tissues. Within this context, genetic identification of phenotype modifiers produced by lack of POMTs functioning and their characterisation would open the doors to an exploration of new diagnostic methods and alternative therapies.

Our main aim is to identify genetic suppressors of the phenotype (muscular and behavioural disorder) resulting from the loss of POMTs function. For this purpose we will initially use genetic tools in Drosophila, where a model of POMT deficiency was previously established. In a second stage, we will move on to a vertebrate modelling system (zebra fish) where we will undertake functional analysis of the identified suppressors. Over the long term, the information obtained in this proposed project may be fundamental in the design of possible gene therapy approaches to suppress CMDs or relieve their symptoms.