Study of Biomarkers That Predict the Evolution of Huntington's Disease

Study Overview
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Brief Summary
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Huntington's disease (HD) is a rare, autosomal dominant, progressive neurodegenerative disorder typically becoming noticeable in middle age. It is clinically characterized by progressive involuntary movements (bradykinesia and hyperkinesia), neuropsychiatric disturbances (depression, irritability), and cognitive impairments progressing to dementia. The striatum (caudate and putamen) is the primary area of neuronal degeneration in HD. Today, there is no validated curative treatment. HD affects approximately 6 000 patients in France and more than 30 000 individuals are considered at risk for this disease. While the disease gene is discovered and we are capable to do a predictive genetic diagnosis for asymptomatic patients, there is no clinical or biological way to predict the age of onset or the progressive profile of patients. One of the fundamental characteristics of this disease is its extreme variability from one patient to other both in terms of their evolution and their onset of action. Thus, this inter-individual variability severely limits the genetic counselling and complicating the neurological assessment. Increasingly, it has been assumed that modifier genes may be the source of this inter-individual variability and that their identification could help the understanding and prediction of disease progression. Given that the mutant protein is ubiquitous, the molecular dysfunction of neurons could be found in peripheral cells from the bloodstream and will be more accessible to investigation.

Detailed Description
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In this context, we propose to focus our research not only on biological and genetic markers but also on neuroimaging and neuropsychological markers using paradigms of time reactions or measurement of evoked potentials. We hope to identify sensitive markers of the degenerative process of Huntington's disease even when patients carrying the gene may or may not have reported the disease. The project is centered on 2 axes: identification of the genetic polymorphism which may explain the phenotypic variability seeing in Huntington's disease identification of biological, genetic and imaging biomarkers that could be used as predictors of clinical progression of Huntington's disease This research is based on the existence of a well followed and well characterized cohort of patients through the Francophone Huntington Network (RESEAU HUNTINGTON de LANGUE FRANCAISE, RHLF). Therefore, this will help to combine the clinical and biological expertise of RHLF.

Official Title
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Study of Biomarkers That Predict the Evolution of Huntington's Disease

Conditions
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Huntington Disease

Intervention / Treatment
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* Other: Huntington patient evaluation
* Other: Healthy subject evaluation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (patient): Voluntary patients symptomatic or asymptomatic Patient with a number of CAG ≥36) Patient who know his genetic status Age greater than 18 years or equal to 18 years Patient who provided written informed consent Exclusion Criteria (patient): - Deterioration of the protocol preventing the understanding of the protocol Inclusion Criteria (control): Voluntary controls with no family history of huntington's disease Control with a number of CAG <36 Age greater than 18 years or equal to 18 years Control who provided written informed consent Exclusion Criteria (control): - Deterioration of the protocol preventing the understanding of the protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patient<br>Voluntary Huntington patients symptomatic or asymptomatic, with a number of nucleotide expansion(CAG) ≥36 and who know their genetic status | Other: Huntington patient evaluation<br>* Neurological, neuropsychological, neuroimaging evaluation and biological sample<br>|
| Healthy subject<br>Voluntary controls with no family history of huntington's disease | Other: Healthy subject evaluation<br>* Neurological, neuropsychological, neuroimaging evaluation and biological sample<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Unified Huntington Disease Rating Scale (UHDRS) | The period of follow-up will achieve at the end of 2020 | up to 9 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mattis Dementia Rating Scale | The period of follow-up will achieve at the end of 2020 | up to 9 years | 
| Trail Making test A et B | The period of follow-up will achieve at the end of 2020 | up to 9 years | 
| Hopkins Verbal Learning Test | The period of follow-up will achieve at the end of 2020 | up to 9 years | 
| Categorical Fluency | The period of follow-up will achieve at the end of 2020 | up to 9 years | 
| Language tests | The period of follow-up will achieve at the end of 2020 | up to 9 years | 
| Social cognition tests | The period of follow-up will achieve at the end of 2020 | up to 9 years | 
| Comportment scale | The period of follow-up will achieve at the end of 2020 | up to 9 years | 
| Neuroimaging | The period of follow-up will achieve at the end of 2020 | up to 9 years | 
| Neuropsychological evaluation | The period of follow-up will achieve at the end of 2020 | up to 9 years | 
| Electrophysiological tests | The period of follow-up will achieve at the end of 2020 | up to 9 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biomarkers, Genetic polymorphism, Neuroimaging markers, Neuropsychology