Enroll-HD: A Prospective Registry Study in a Global Huntington*s Disease Cohort

Huntington*s disease (HD) is an autosomal dominant neurodegenerative disorder
that results from an unstable expansion of the trinucleotide repeat CAG in the
HD gene IT-15. HD has a prevalence of 5-10 per 100.000 in the general
population. The clinical features of HD usually emerge in adulthood (mean age
of onset is 40 years) with movement disorders, cognitive dysfunction and
psychiatric symptoms. The course of HD is relentless, leading to functional
disability and death over a period of 10-20 years. With genetic testing
(following genetic counseling) it is possible to predict that a person will
develop HD a long time before clinical symptoms and signs develop. To date,
there is no treatment that has been shown to alter the progression of the
disease. Benefical effects have been reported when applied in model systems of
HD but the predictive value of these results for patients are yet unknown. As
HD is a rare disease, extensive cooperation is essential to be able to include
the number of participants required for conclusion well powered studies.

Objective 1: To improve the understanding of the dynamic phenotypic spectrum
and the disease mechanisms of HD by:
a. collecting natural history data covering the cognitive, behavioral and motor
domains permitting estimates of rates of progression in
HD and allowing insights into the neurobiology of HD,
b. collecting data and biologic samples to identify genetic
and environmental factors influencing and/or modifying the HD
phenotype and disease progression, and
c. promoting interrogatory studies that may provide clues to the pathogenesis
of HD.

Objective 2: To promote the development of evidence-based guidelines to inform
clinical decision making and improve health outcomes for the participant/family
unit by:
a. assisting in the identification of beneficial interventions (clinical,
pharmaco-therapeutic, non-pharmacologic),
b. facilitating the dissemination and implementation of
currently
proposed best clinical practices,
c. providing a platform for conducting outcome research, and
d. promoting exploratory data analysis projects that may
identify processes to further improve the healthcare of affected
individuals and their families.

Objective 3: To provide a platform to support the design and conduct of
clinical trials by:
a. providing a resource to identify, develop and qualify
novel assessment tools, clinical endpoints and biomarkers,
b. collecting longitudinal data to inform disease modeling
studies, and
c. facilitating the identification of potential trial
participants informing the selection of potential trial participants using data
to
estimate and quantify slopes/rates of disease
progression (providing *run-in* data).

To achieve these objectives suitably de-identified and coded clinical
information and biological samples collected from study participants will be
made available to investigators for research purposes in accordance with
procedures adopted by the steering committee.

Enroll-HD is an observational, prospective, multi-national, multi-centre study
without experimental treatment.

Since Enroll-HD is an observational study, participants do not undergo specific
risks by participating. Their burden is limited to a minimum as the evaluations
occur within or immediately after the ambulant care of the Neurology department
on a regular basis. Participants will receive no immediate benefit from
participation in this study. The only potential benefit is a better
understanding of HD and the possibility that the information obtained in this
study lead to potential treatments and to plan future research studies of
experimental drugs aimed at slowing disease progression or postponing the onset
of HD.