Huntington’s disease Research Networks in the UK Dr Olivia Handley & Dr Jenny Naji School of Biosciences, Cardiff

1. Huntington’s disease Research Networks in the UKDr Olivia Handley & Dr Jenny NajiSchool of Biosciences, Cardiff University

2. UK HD Networks • EHDN • UKHDN • UKHDN as part of DeNDroN

3. UKHDN • Inaugural meeting January 2003 • 2007 meeting: April 25th-26th, Cardiff • UK clinicians and scientists with an interest in HD to work towards effective management and treatment of people at-risk of, and affected by HD Aims • Establish a large cohort of well-characterised patients with a view to rapid implementation of clinical trials • Facilitate clinical studies aimed at increasing understanding of the pathogenic processes underlying the neural damage seen in HD Objectives • Facilitate collaborative national and European research initiatives • Discussion of relevant scientific findings, and mediated the development and review of ethical considerations surrounding research and clinical management of HD.

4. Aberdeen • Belfast • Birmingham • Cambridge • Cardiff • Dundee • Edinburgh • Exeter (4 satellite sites) • Fife • Glasgow • Gloucester • Guy’s and St Thomas, London • Hammersmith, London • Hull • Leeds • Leicester • Liverpool • Manchester • Newcastle-upon-Tyne • NHNN, London • Oxford • Plymouth • Putney, London • Sheffield (5 satellite sites) • Southampton • St Georges, London • Stoke UKHDN

5. CARDIFF Coordination centre for the UKHDN and the English speaking arm of the EHDN Network

6. Euro-HD Network www.euro-hd.net Aims • Provide a platform for professionals, people affected by HD and their relatives to facilitate working together throughout Europe • Facilitate epidemiological and interventional trials meeting GCP standards • Large numbers of participants to run valid clinical trials

7. What is the EHDN? • Constitution • Executive committee • Scientific committee • Registry committee • ‘Registry’ • Clinical database • Biobank • Working groups • Scientific resource • Proposals • Library

8. Who finances the EHDN? • The High-Q Foundation in the context of sponsoring ‘The Huntington Project’, a 10-year endeavour to speed up the process of finding treatments to improve the natural course of HD • Funding for coordination, working groups, database

9. Advantages of participating • Detailed standardised longitudinal clinical data in an electronic format • Registry of a large number of HD patients wanting to be involved in clinical research • Easier access to research for participants

10. Organisation Central Co-ordination IT Language Coordinators Study Sites Huntington’s associations HD patients Bernhard Landwehrmeyer

11. Working groups • Novel Assessment (motor, cognitive, behavioural) • Standard of Care • Quality of Life • Health Economics • Biomarkers • Imaging • Brain banking • Genetic modifiers • Neuroprotective strategies • Surgical techniques • Symptomatic treatment • Juvenile HD

12. English-speaking Coordination Coordinators: Jenny Naji and Olivia Handley • Liaise with central co-ordination • Liaise with UK sites • EHDN reports • Train UK sites for ‘Registry study’ • Facilitate ethical/R and D approval procedure • Monitor data collection- plausibility and correctness • Maintain Euro-HD website • Working group membership

13. Registry • Objectives: • Identify those interested and available to participate in studies • How are affected people and their relatives are coping? • Establish phenotypical characteristics of the European HD population.

14. Registry • Assessment protocol • UHDRS • Motor • Psychiatry • Neuropsychology • CAG repeat length • Medical history including list of comorbid conditions • Medication • Total Functional Capacity • Becks Depression Inventory • Hamilton Depression Scale • Health Economics questionnaire • Caregiver questionnaire • SF-36 • Biosamples • FHQ

15. Optional components • CAG genotyping • Genetic modifiers and establishing biomarkers to track the progressive course of HD • 10ml to generate lymphoblastoid cell lines: inexhaustible resource for future research into genetic modifiers of HD. • 10ml used to remove the lymphocytes and plasma. Lymphocytes cryopreserved, backup if cell lines fail, and for use in functional + RNA & protein studies. • Family history • Permission to be contacted between visits

16. Participation in Registry? • Gene positive patients with/without symptoms of HD • Core/Extended clinical assessment • Biosamples • Family History • Permission to be contacted • Companions (of 1) • Questionnaires • Family History • Control participants (may also be 2) • Brief clinical assessment • Biosamples • Permission to be contacted

17. Progress- UK studies • Establish a cohort through Registry • Progress: 1961 patients, UK = 623, with 11120 forms (14 sites) • Introduce interventional trials • Pharmaceutical sponsors: Amarin, UK 7 sites • Epidemiological studies • Juvenile HD • Development of assessment tools • Neuropsychiatry: develop behavioural UHDRS, looking at PBA • Juvenile HD: Juvenile HD UHDRS scale • Motor : training video

18. Presymptomatic HD clinic Prof Anne Rosser: Consultant Neurologist Prof Angus Clarke: Consultant Geneticist Ruth Glew: Genetics Nurse Counsellor Cardiff HD clinic HD Management clinic Prof Anne Rosser: Consultant Neurologist Dr Jon Bisson: Consultant Psychiatry Dr Jenny Naji: Research Associate Dr Olivia Handley: Research Associate Kathy Price: Research Nurse Lynda Ellison-Rose: Research Nurse South Wales HD clinical research projects Collaborative projects: Local projects: NEST-HD Sleep and circadian rhythm Registry Language and HD PREDICT-HD Capacity and decision making in HD Amarin Mobility and HD Biomarkers in HD

19. THE END Questions?