Energy crisis in muscle cells - genetics and pathogenesis

The goals of this precision medicine project are to characterize the pathogenesis of new glycogen storage diseases discovered by us and to investigate the molecular background of the mitochondrial dysfunction in inflammatory muscle diseases.We have recently discovered and described four different genetic diseases with storage of polyglucosan, composed of a starch-like polysaccharide and various proteins.

One of these diseases is of special interest since we demonstrated that lack of glycogenin-1, the primer for glycogen synthesis, cause abnormal storage of polyglucosan.

These patients suffer from muscle weakness and/or heart failure.Biopsy material that is already collected from well characterized patients is studied by molecular biological methods.

By laser micro-dissection, entire cells or protein aggregates of interest are isolated for analysis by mass spectrometry or quantitative PCR.

Mitochondrial DNA abnormalities are studied in detail using deep next generation sequencing applying a novel pipeline developed in Gothenburg (MitoSAlt).

Characterization of the storage of polyglucosan is important for therapeutic strategies e.g. delivery of compounds to the affected cells in order to remove the deleterious storage material or applying the evolving oligonucleotide treatment strategy.

Mitochondrial deficiency in inflammatory myopathies needs to be characterized to understand the pathophysiology and since treatment may take advantage of progress in mitochondrial medicine.