Grant: CIHR Fellowship

Huntington disease (HD) is an inherited neurodegenerative disorder that affects a person's mental and physical abilities usually during adulthood. This disorder is caused by a faulty gene that leads to the production of a toxic protein - mutant huntingtin (HTT) - and causes a progressive loss of nerve cells in the brain. HD is often described as having Alzheimer's, Parkinson's and Amyotrophic lateral sclerosis diseases all at once, as it manifests with a combination of motor dysfunction, behavior changes and cognitive decline, similar to these other neurodegenerative diseases. Currently, there are no treatments that can cure or slow down the progression of the disease. Scientists and physicians often use biomarkers, biological molecules present in blood and spinal fluid (liquid that surrounds the brain), to monitor disease progression and evaluate how patients respond to disease treatments. One potential biomarker is extracellular vesicles (EVs), small membrane-enclosed sacs that are released from nerve cells in the brain into the bloodstream. EVs carry information, such as proteins and genetic material, that reflects brain health but also disease state. Interestingly, HTT is released from nerve cells in these small sacs, highlighting EVs potential as a window into the brain. Our project aims to characterize and measure HTT levels in vesicles isolated from blood as a biomarker for assessing disease progression in the brain and HTT lowering therapies. Comparison of HTT levels in EVs to disease measures will indicate how vesicles in circulation reflect disease-related changes. Furthermore, assessment of HTT levels in blood-derived vesicles will give us a more accessible biomarker and facilitate the access to human samples since spinal fluid collection, which is currently used in HTT lowering clinical trials, is an invasive outpatient procedure.