B002 The Dutch CureQ consortium: using IPSC modelling and clinical and biomarker data from patients to predict, delay and cure polyglutamine caused neurodegeneration

<h3>Introduction</h3> Spinocerebellar ataxia (SCA) type 1 and 3 and Huntington disease (HD) are caused by CAG repeat expansions within relevant genes. Novel promising therapeutic developments have raised new and urgent questions. 1) the optimal time to start treatment. 2) can we derive patient-tailored predictions. 3) can less invasive strategies be developed to lower mutant protein. 4) can we prediction onset and progression of disease in an ethically sound way. <h3>Methods</h3> We will create isogenic human-derived cells with different CAG repeat lengths for SCA1, SCA3 and HD in work package (WP) 1 and develop robust platforms to characterize amphenotypic landscape whilst differentiating them into 2D 3D models. In parallel, we will generate these landscapes for iPSC-models derived from cells from actual patients with known ages at onset to find landscape-derived parameters predicting disease onset (WP2) combined with clinical, imaging and fluid biomarkers (WP3). These landscapes will be used to evaluate newly-developed therapeutic strategies (WP4). Finally we will study the ethical implications of such improved diagnostics (WP6) Discussion and <h3>Conclusion</h3> With our consortium of academic and biotech researchers, clinicians, ethics experts and patient communities we hope to provide robust and sensitive phenotypic, cell biological readouts for a proper and responsible implementation of patient-tailored prediction of disease onset, disease course and severity. These will aid clinical and personal decision-making on presymptomatic testing and life planning by at-risk individuals.