HD usually progresses slowly, and symptoms vary from person to person. At the present we cannot tell which symptoms a person with the HD gene will get, or when. The clinical assessments used currently to measure disease progression are not accurate enough. This is an important issue for the evaluation of possible treatments for HD. For instance, therapies that slow down disease progression would need clinical trials involving hundreds of patients over many years. This scenario becomes more complex when we consider HD gene carriers who have no symptoms at all. Dozens of treatments may need to be tested in the next few years. We therefore need ways to reduce the number of participants and duration of clinical trials. We hope that biomarkers will help us identify the most promising drugs.
The Biomarkers Working Group aims to find biomarkers for HD and develop a biomarker-based clinical trial infrastructure. In particular, the aims of the working group are:
To identify and validate biomarkers that can be used to track disease progression, detect disease-related changes and monitor treatments that may delay onset of HD.
To encourage collaborative HD biomarker research by facilitating sharing of ideas, samples, techniques and results.
To establish and conduct major HD biomarker research projects that will delineate the infrastructure and assessment protocols for future clinical trials.
To share best practice in biomarkers and HD assessment tools with other complementary groups and organisations, both within EHDN and beyond.
Our working group enjoys fruitful collaborative links with other EHDN Working Groups, especially the Motor Phenotype WG (quantitative motor markers), the Cognitive Phenotype WG (accurate cognitive assessment tools), the Genetic Modifiers WG (investigation of known genetic modifiers as potential biomarkers and known biomarkers as potential genetic modifiers) and the Imaging WG (developing and cross-validating imaging measures as biomarkers). We have numerous worldwide collaborations, especially within the scope of the Predict-HD Study and other Huntington Study Group projects, the HD-Toolkit Project (working towards evidence-based review of HD outcome measures) and the Huntington’s Disease Neuroimaging Initiative (HDNI).
The Biomarkers Working Group focuses on the following projects:
Collection and biobanking of biomarker samples that can be used for multiple biomarker projects.
Cross-sectional and longitudinal biomarker discovery projects.
Cross-sectional and longitudinal biomarker validation projects.
TRACK-HD: the Biomarkers Working Group’s flagship multi-centre biomarker evaluation project.
TRACK-HD is a major international study that aims to determine what combination of measures is the most sensitive for detecting change over the natural course of pre-manifest and early HD, and validate these as potential outcome measures for use in future therapeutic trials.
EHDN REGISTRY: We helped to design and test the biomarker component of the REGISTRY Project and are closely involved in the analysis of the results.
The members of our working group are involved in many projects, including:
Investigation of inflammatory changes in HD (led by Sarah Tabrizi, London)
Investigation of cholesterol metabolites as biomarkers (Stefano Di Donato, Milano)
Brain-derived neurotrophic factor (BDNF) as a potential biomarker (Elena Cattaneo, Milano)
Gene expression markers (Hoa Nguyen, Tübingen, and Borut Peterlin, Ljubljana)
Metabolic markers (Roger Barker, Cambridge, and Alexandra Dürr, Paris)
Huntingtin aggregates as possible biomarkers (Gill Bates, London, and Novartis PLC)
in biomarkers projects is a very useful way to help us all move closer
to treatments that will slow down the progression of HD. You can be as
involved as you like: Some studies require only a urine sample, while
others involve regular or more detailed assessments, with longer
sessions and collection of more samples (such as blood). Patients
enrolled at any EHDN-associated centre are likely to be able to enrol
in at least one project (REGISTRY), which includes a biomarker research
component. Some individual centres have specific biomarker projects
active in addition, and will inform potential subjects directly. Most
participants are recruited through HD clinics. Some centres have their
own sources of information, such as websites or HDA bulletin boards,
which patients can use to volunteer for studies. Most biomarker
studies involve the donation of at least one sample of urine, blood or
other tissue, such as spinal fluid or muscle. In addition, most studies
will require basic clinical information, such as the result of an HD
genetic test, what symptoms you have and how long you have had them,
and what medicines you are taking. Some studies are much more detailed
and collect information like family history and questions about your
mood. The frequency of the visits varies greatly. Some studies are
one-offs, so your involvement is over when you have donated a sample of
urine or blood. Others (like TRACK-HD) involve regular follow-up
visits, usually once a year. All research of Biomarkers Working
Group members carries the ethical approval of local and national
research ethics committees. This includes requirements for proper data
protection, such as the use of pseudonyms.
Biomarkers Working Group has 122 regular members and 55 honorary
members (June 2008). Membership is open to all researchers involved in
HD biomarker research, including researchers actively involved in
collecting biosamples for the REGISTRY Study, as well as those with
individual or collaborative biomarker projects. In addition, membership
applications are encouraged from researchers with interests related to
biomarker identification and validation, such as bioinformaticians or
researchers with perspectives on biomarker research from other disease
areas and from the industry. From time to time, we offer regular or
honorary membership to researchers from other disciplines (such as
neuroimaging, statistics and motor assessment). Working Group members
are encouraged to present and discuss their projects and findings at
our regular face-to-face meetings. These are held every 6 to 12 months.
Dr. Edward Wild
Prüfarzt, Motorische Beurteilung National Hospital for Neurology and Nerosurgery, Department of Neurodegenerative Disease, Institute of Neurology