University Clinics UPD

Research groups

Group Orth

Projects

Currently, there are ongoing studies in the following domains:

The extended metabolic phenotype of preclinical Huntington’s disease: Whole body PET studies of glucose metabolism (funded by the SNSF)

This project explores the relationship between brain structure, brain function, glucose metabolism and behaviour in Huntington’s disease, a hereditary neurodegenerative disease. The goal is to better understand what happens just before people carrying the HD mutation develop clinical signs of manifest HD. This can help to better predict the age at onset and improve the timing of disease modifying interventions. The current project is a collaboration with the Department of Nuclear Medicine at Inselspital Bern (head Prof Axel Rominger), Prof Jessica Peter at University Hospital for Old Age Psychiatry and Psychotherapy and Prof Christian Wolf, Department of Psychiatry, Heidelberg University Hospital, Germany. We will examine carriers of the HD mutation who have no clinical signs of HD. They will undergo a whole-body glucose PET, and structural and resting state functional 3T MRI. The main question is whether HD mutation carriers differ from healthy volunteers in dynamic glucose uptake in the brain and/or peripheral tissues like skeletal muscle, and, if so, if there is a relationship between glucose metabolism and structural, or functional, changes in the brain. The project employs state-of-the-art PET and MRI methods, and multi-modal biostatistical methods for data analysis.

Prediction of cognitive involvement in de-novo Parkinson’s disease

This project is based on the clinical impression that “parkinsonism” comprises a heterogenous group of patients not all of whom have idiopathic Parkinson’s disease. We hypothesise that different subgroups can be distinguished based on the evolution of cognitive performance over time. The goal is to be able to predict in patients with de-novo Parkinsonism which cognitive subgroup they will eventually belong to. To this end, we use the PPMI database and advanced biostatistical modelling.

The landscape for delivering novel therapies in Huntington’s disease (funded by Roche)

We are proposing a European project with the aim of preparing the HD community for when novel therapies will become available. Specifically, the present project will provide data about

  1. The prevalence of HD (according to definition) in Europe and at country level. This information is important for knowing how many people might be eligible for a given novel treatment
  2. The structure of HD care in three countries (Switzerland, United Kingdom, Spain)
  3. Capacity for different delivery options, e.g. intrathecal or surgical
  4. How HD experts operate in each three countries (Switzerland, United Kingdom, Spain)
  5. The health care system in which HD care is delivered in each of the three countries
  6. Reimbursement rules and legal aspects of health care in each of the three countries

Based on the data described above we will be able to understand better how health care systems operate and HD patients/families are cared for in each country. We will know better what the ‘HD landscape’ looks like in each country including patient flow, capacity, HD expertise, organization of HD experts, reimbursement and legal background. The data will be used to develop models to estimate the number of eligible patients per country taking into consideration the definition of prevalence according to the envisioned scenario. For instance, if drug A were licensed for patients with TFC stages 1 and 2, then this definition of ‘HD’ would form the epidemiological basis for the model. If drug B were licensed for people carrying the HD gene (premanifest HD) this would be the definition of ‘HD’ for that scenario. Against these models that calculate hypothetical scenarios we will obtain data on the current status, i.e. how many people with ‘HD’ are currently cared for and where. Knowing how many people are actually being cared for and how many we expect there to be according to the estimates from prevalence models will allow to estimate the number of people in the respective countries who are unaccounted for.

Genetic modifiers of Huntington's Disease

The CAG repeat expansion mutation explains about half of the variation in important clinical expressions of HD, such as the age-at-onset of unequivocal motor signs. Work of the Genetic Modifiers in HD (GeM-HD) consortium has shown that other genes can modify how the biology of HD unfolds.  This work can potentially identify novel targets for disease modification.