PhD defence R. (Rodrigo) Cañibano Fraile

Dissertation in short:

The purpose of this thesis is to study the molecular mechanisms that drive Pompe disease, as well as to investigate strategies to enhance muscle regeneration; ultimately aimed at the development of regenerative therapies for muscle disorders. We humbly hope that the work of this thesis contributes to the fulfilment of these goals in the future. In chapter 1, we described fundamental notions of Pompe disease. In chapter 2, the metabolism of glycogen in muscle and brain of mouse and skeletal muscle of human patients with Pompe disease were analyzed. In chapter 3, recent progress on the role of satellite-cell mediated repair in neuromuscular disorders was reviewed, with an emphasis in Pompe disease. In chapter 4, an in vitro assay for the evaluation of satellite cell activation through ex vivo isolation of murine skeletal muscle fibers was presented. In chapter 5, the relationship between autophagy dysregulation, satellite cell activation, and regeneration was investigated in a mouse model of Pompe disease. In chapter 6, we described a method to isolate murine regenerative myogenic cell fractions - termed reserve cells - from ex vivoo-expanded muscle cultures with capacity to regenerate skeletal muscle in vivo upon transplantation. In chapter 7 we discussed the results of this thesis.