Main aim: To generate a collection of biosamples from deeply phenotyped patients and carriers with Huntington’s Disease (HD) and Spinocerebellar ataxia (SCA) types 1 and 3, all so-called polyQ diseases, from the entire disease spectrum and expansion range. To achieve this, data and samples will be collected from existing resources, complemented with data and samples obtained from newly recruited subjects.
WP Leader: Bart van de Warrenburg (Radboudumc)
Objectives: Existing data and sample collections in HD, SCA1, and SCA3 often lack carriers of CAG repeat expansions at the two extreme ends: those with intermediate expansions who often present with late-onset and mild disease for SCA, and generally no clinical signs for HD, and those with very large expansions who may manifest early (even juvenile) onset and severe phenotype for both diseases. We will set up a longitudinal study that specifically targets these two groups, for the three different polyQ diseases. In order to deep phenotype these participants, we will measure a rich set of clinical outcomes, and correlate these with known and new biomarkers in blood and cerebrospinal fluid (CSF), and with Magnetic Resonance Imaging (MRI) markers. Participants will undergo three measurements, with one-year intervals. We aim to find biomarkers that are sensitive to change over time, and we expect to find differences in these biomarkers between the different groups.
In addition, our effort will provide WPs 1, 3 and 4 with donor cells from selected individuals from different patient categories, and our resources will also testing of hypotheses generated by these preclinical WP’s.