Grant: Operating Grant: Joint Programme on Neurodegenerative Disease Research (JPND)

Huntington's disease (HD) is fatal condition that affects the brain, leading to both mental and physical deterioration over time. HD is caused by a defect in a specific gene, which results in an abnormal version of a protein called huntingtin. Although we know this, attempts to combat the disease by reducing this abnormal protein haven't been successful so far. Interestingly, the timing of when symptoms first appear in HD patients seems to be related to variations within the huntingtin gene. However, how these genetic variations affect disease development or progress is not understood. Our team aims to address this gap by investigating the role of these genetic variations in the development of HD. We will be studying groups of HD patients from different populations and also using new animal and cell-based models of HD. This will help us understand how these genetic variations influence the disease and improve the accuracy of diagnostic tests. This information will also be invaluable in genetic counseling, helping to predict the likely progression of the disease in individual patients. It will also help to define specific subtypes of HD, which will make future clinical trials more targeted and effective. To explore how these genetic variations impact the disease at the cellular level, our delCAA consortium which brings together leading international research laboratories each with unique expertise in different aspects of HD, will perform experiments using various cell models as well as animal models. By doing so, we aim to establish a clear connection between these genetic variations and the development and progression of HD. Through our collaborative efforts, we hope to bring about meaningful advances in understanding and treating this devastating disease.