Myotonic dystrophy type 1 is a severe inherited muscle disease without a curative treatment. This thesis focuses on developing a genetically modified cell therapy based on muscle stem cells called pericytes. We showed that pericytes from DM1 patients can be efficiently isolated and expanded into large numbers of cells capable of forming muscle fibers in culture, despite the presence of DM1-related abnormalities. These disease features in DM1 muscle fibers improved when healthy pericytes were added, even in relatively small amounts. Using CRISPR/Cas9, we successfully removed the pathogenic DNA change in DM1 pericytes, which eliminated disease features while preserving cell growth and identity in vitro. Mouse studies further demonstrated that healthy human pericytes contribute to muscle regeneration after direct injection into muscle tissue. Together, these findings indicate that pericytes are a promising basis for future genetically modified cell therapy for DM1. Further research is needed to assess safety and efficacy.
Renée Buurman Raaijmakers (1992) studied Psychology and Cognitive Neuroscience at Radboud University, completing research on epilepsy and memory. Inspired by neurogenetics, she joined Human Genetics, where she co wrote a PhD grant awarded in 2018. Her PhD and postdoctoral work, funded by the Prinses Beatrix Spierfonds, focuses on developing a gene edited, pericyte based therapy for myotonic dystrophy type 1.