Regulation of transcription in Huntington's Disease

The genetic cause of Huntington's disease was identified 15 years ago. All people who go on to develop the devastating and progressive physical, emotional and mental symptoms of Huntington's disease have one copy of the gene that encodes an important protein called huntingtin which is slightly different in sequence from the normal copy of the gene that every person expresses. It is absolutely clear that the protein encoded by the abnormal huntingtin gene directly causes Huntington's disease. It is not known how mutant huntingtin initiates the deleterious changes in brain cells that occur over decades. Scientists are actively testing compounds in test tubes, cells and mouse models of the disease to see how compounds that are now available might alter the disease symptoms. My research is focused on understanding what mutant huntingtin does that directly causes changes in brain cells that lead to disease symptoms. We have studied how mutant huntingtin protein directly changes the way that specific genes are expressed early in the disease. If we can understand how mutant huntingtin interfers with the regulation of gene expression, we may be able to identify new targets for drug development. Potential future HD patients can be easily identified at a very young age before degeneration of the brain occurs. As such, treatments that would delay the time that symptoms start or reduce the severity of the disease could be very effective for this group of patients and their families.