Cohort Research on Wilson's Disease

Study Overview
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Brief Summary
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Wilson's disease (WD) is an inherited disorder that causes abnormal copper accumulation in the brain and/or liver. Some people develop neurological or psychiatric symptoms whereas other develop liver disease. The reasons for this are unclear but genetic factors are likely to contribute. Current treatment, using copper-binding medications, is required lifelong. Some respond well but others suffer debilitating side-effects or deteriorate despite treatment, leading to disability or the need for liver transplantation. In the first part of this study the main aim is to identify genetic factors that determine whether someone with a diagnosis of WD will develop neurological involvement or not. The investigators will invite 500 adults with WD across the UK to take part. Participants will be asked to complete an online questionnaire and provide a saliva sample for genetic testing using a collection kit sent via post. Identifying these genetic factors would significantly advance our understanding of the disease and may provide new targets for drug discovery or help guide more personalised approaches to treatment. In the second part of this study the main aim is to develop new ways to monitor the effect of WD on the brain using tests. Copper levels in blood and urine, currently used to monitor the disease, are unreliable and do not necessarily reflect ongoing brain damage. The role of MRI scans, cerebrospinal fluid tests or other measures of brain damage, commonly used in other neurological disorders, is unclear. The investigators will therefore follow a group of 40 patients using clinical assessments and a combination of neurological tests, including novel imaging and laboratory techniques, over 24 months. Developing new approaches to monitoring the effect of WD on the brain will enable better prevention of neurological disability and be essential for demonstrating the effectiveness of new treatments, such as gene therapy, in clinical trials in the future.

Official Title
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Cohort Research On Wilson's Disease: Genetic Determinants and Biomarker Discovery for Neurological Involvement

Conditions
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Wilson's Disease

Intervention / Treatment
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* Genetic: Next generation sequencing
* Diagnostic Test: Imaging and fluid biomarkers


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (part 1 and part 2): Diagnosed with Wilson's disease Age 16 years or over Living in the UK Exclusion Criteria (part 2): Participant has another medical or psychiatric illness that would interfere in completing assessments Participant is pregnant

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Part 1<br>Genetic determinants (n=500) | Genetic: Next generation sequencing<br>* Saliva samples<br>|
| Part 2<br>Biomarker discovery (n=40) | Diagnostic Test: Imaging and fluid biomarkers<br>* Magnetic resonance imaging of the brain and urine, blood and cerebrospinal fluid sampling<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical phenotype | Responses to online questionnaires for the first part of the study will be used to the determine the presence or absence of neurological symptoms. | Questionnaire responses will be collected over two years. | 
| Unified Wilson's Disease Rating Scale (UWDRS) | Participants in the second part of the study will be assessed at research visits using this scale (0-320) | This assessment will be performed at two research visits 12-18 months apart. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genetic modifiers, Biomarkers