Project name: Delineating the role of HTT Cis-Variants in the pathogenesis of Huntington disease (delCAA-HD)

Project start date: 1. 6. 2024
Project completion date: 31. 5. 2027
Project Budget: EUR 1,100,666, of which EUR 250,750 for VFN, mandatory co-financing from own resources is not required
Project guarantor (workplace): Clinic of Neurology
Identification number of the project at the Ministry of Education and Culture: 9F24002

VFN participates in the project as one of the partners of the international consortium, the main researcher is doc. MD Jiří Klempíř, Ph.D. from the Neurological Clinic. The coordinator of the project is the Department of Human Genetics, Ruhr University Bochum, Germany. Other partner countries include Sweden, Canada and Turkey.

The project is supported under the Joint Programming Initiative "Neurodegenerative Diseases" (JPND 2023) entitled "Large Scale Analysis Of Omics Data For Drug-Target Finding In Neurodegenerative Diseases"

Link to the Ministry of Education's call

Project brief:

Huntington's disease (HN) is an autosomal dominant neurodegenerative disease manifested by involuntary movements, free motor disorders, cognitive deterioration and behavioral changes. HN is caused by a mutation in the gene for the huntingtin protein. Attempts to reduce the production of this abnormal protein have not yet been successful. It is still not clear by which mechanisms mutated huntingtin affects the onset and/or course of the disease. Our team wants to close this gap by investigating the role of genetic mutation variation in the development of HN. We will study groups of HN patients from different populations as well as use new animal and cellular models of HD. This will help us understand how these genetic variations affect disease. This information can be useful in genetic counseling as it helps to predict the likely development of the disease in individual patients. They will also help define some subtypes of HN. We assume that our findings will enable more targeted and effective clinical trials in the future. Our delCAA consortium, which brings together leading international research laboratories, each with unique expertise in different aspects of HN, will conduct experiments using different cellular models to explore how these genetic variations affect the disease at the cellular level. In this way, we want to establish a clear connection between these genetic variations and the development and progression of HN. We hope that our collective efforts will make significant progress in understanding and treating this fatal disease.

Project details:

Huntington's disease (HD) is a 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 have not 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 counselling, 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.