Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Rosanne Ausems (Donders series 550)

25 April 2022

Promotors: prof. dr. J.H.L.M. van Bokhoven, prof. dr. B.G.M. van Engelen
Co-promotor: dr. D.G. Wansink

First steps towards a pericyte-based muscle therapy for myotonic dystrophy

Progressive wasting of skeletal muscle is characteristic for a subgroup of myopathies, the genetic and progressive conditions collectively called muscular dystrophies (MDs). I explored the possibility of a cell-based therapy to combat muscle atrophy in a specific muscular dystrophy called myotonic dystrophy type 1 (DM1). In DM1 a (CTG)n-repeat expansion in the 3’ untranslated region of the DMPK gene causes the formation of toxic RNA which sequesters proteins, such as MBNL1, which function in transcription, splicing and RNA export. The accompanying disturbances in cell metabolism lead to myotonia and progressive muscle weakness and wasting. I successfully isolated a distinct class of myogenic progenitors, called pericytes, from skeletal muscle of transgenic mice and from DM1 patients. Pericytes showed promising results in vitro and crucially in vivo for the treatment of DM1. With this research, we took the first steps towards pericyte-based muscle therapy for myotonic dystrophy.