Huntington’s disease (HD) is a progressive autosomal dominant neurodegenerative disorder with a broad spectrum of clinical features. The disease is caused by a mutation in the Huntingtin gene (HTT... Show moreHuntington’s disease (HD) is a progressive autosomal dominant neurodegenerative disorder with a broad spectrum of clinical features. The disease is caused by a mutation in the Huntingtin gene (HTT) on the short arm of chromosome 4. In September 2015, the first-in-human study looking into the safety of an intrathecally administered antisense oligonucleotide therapy to reduce mutant HTT (mHTT) protein was launched in HD patients, where the drug proved to be safe and the intended mHTT lowering was demonstrated. The aim of this thesis is to find biomarkers corresponding with disease state and measuring progression in different stages of HD, which in turn can be used as suitable objective surrogate clinical trial endpoints. We put special emphasis on longitudinal study designs, as these provide the most useful clinical progression and parameter change associations. Although previous neuroimaging studies have shown potential markers, findings remain inconsistent or lacking association with disease state. As such, further exploration of neuroimaging techniques is of great relevance. Using different approaches to evaluate the potential usefulness of specific markers, we demonstrate biomarkers that may assist in the objective assessment of a potential disease-modifying intervention. Show less
The aim of this thesis is to examine employment and driving ability in gene carriers with Huntington’s disease (HD). HD is an autosomal-dominant inherited neurodegenerative disorder and manifests... Show moreThe aim of this thesis is to examine employment and driving ability in gene carriers with Huntington’s disease (HD). HD is an autosomal-dominant inherited neurodegenerative disorder and manifests during mid adulthood. The disease is clinically characterized by motor disturbances, cognitive decline and behavioral changes. Since there is currently no cure for HD, the focus of treatment is on improving quality of life and providing the necessary support to patients and families. Maintaining independence through employment and driving, for as long and as safely as possible, has a substantial influence on a patient’s general functioning. Our results consistently showed that the cognitive and behavioral changes of HD are more debilitating in daily life than the characteristic motor signs, and are associated with employment and driving a car. Healthcare professionals should be educated about HD to allow them to provide appropriate information to patients and families when discussing possible changes in working and driving as a result of HD. Individual evaluation of driving ability is warranted and the recommendation to stop driving should not solely be based on disease stage or a genetic confirmation. Multidisciplinary screening, using a HD-specific test battery, is recommended and should be embedded in the clinic. Show less
