Investigating the relationship between HTT CAG repeats, somatic instability and neuronal dysfunction in Huntington’s Disease using a highly parallel stem cell-based single cell approach.

Our proposal aims at understanding one of the most fundamental mechanisms of the pathogenesis of Huntington's Disease (HD), a rare genetic condition characterised by the progressive degeneration of specific brain regions of the brain that affects many families. Our study has two primary objectives:

First, we aim to test the theory suggesting that HD develops in two stages. Initially, there is a non-toxic pathological genetic change in the affected cells, inherited from one of the parents. Over time, this genetic change becomes unstable and increases in size within brain cells, leading to the progression and its manifestation later in life. Our plan involves conducting experiments to determine when this change becomes harmful and how it impacts the most vulnerable cells of the brain. This knowledge could help us find the best way to stop the disease before it manifests. We will use human embryonic stem cells and advanced scientific techniques to examine individual brain cells and the specific genetic changes that occur in brain neurons over time in a controlled in vitro environment.

Our research could provide a better understanding of the molecular mechanism underlying the manifestation of HD and reveal new targets for treatment. If our work is successful, it could lead to improved therapies, giving HD patients and their families a more promising future.