Bo Porse
A human cell culture model for the assessment and targeting of CAG repeat length expansion in Huntington´s Disease
Huntington’s disease (HD) is a progressive neurodegenerative disorder developing as a result of a specific CAG repeat expansion in the HTT gene encoding for the ubiquitous huntingtin protein. The development of HD treatment modalities has generally focused on targeting mutated HTT protein (or mRNA), but have not been successful.
HD patients are born with a CAG repeat number of >40 and it has been shown that this number expand over life. Strikingly, disease onset does not occur before repeat numbers exceed 500 in very specific neuronal subset. Here, we will generate a cell culture model of these neurons and assess if we can monitor repeat extension over time. If so, we will use this model to screen for drugs that can delay repeat expansion, potentially beyond human lifetime, thereby preventing HD onset.
