Huntington's disease (HD), first described by George Huntington in 1872 and previously known as Huntington’s chorea, is a neurodegenerative genetic disorder that causes psychiatric problems, affects muscle coordination, and leads to severe cognitive decline. Physical symptoms of HD can begin at any age from infancy to old age, but usually begin between 35 and 44 years of age. The disease is caused by an autosomal dominant mutation in either of an individual's two copies of their huntingtin gene, meaning each child of an affected parent has a 50% risk of inheriting the disease. Expansion of a CAG triplet repeat stretch within the huntingtin gene produces a mutant form of the huntingtin protein containing an expanded glutamine repeat, which gradually damages cells in the brain through currently unknown mechanisms that are the focus of intense global research to define and effectively treat the illness.
CHDI Foundation, Inc. is a privately-funded, not-for-profit, biomedical research organization that is exclusively dedicated to rapidly discovering and developing therapies that slow the progression of Huntington’s disease (HD). Our scientists work closely with a network of more than 600 researchers in academic and industrial laboratories around the world in the pursuit of these novel therapies, providing strategic scientific direction to ensure that our common goals remain in focus. This helps bridge the translational gap that often exists between academic and industrial research pursuits and that adds costly delays to therapy development. In its role as a collaborative enabler, CHDI seeks to bring the right partners together to identify and address critical scientific issues and move drug candidates to clinical evaluation as rapidly as possible. Our activities extend from exploratory biology to the identification and validation of therapeutic targets, and from drug discovery and development to clinical studies and trials.
The European HD Network (EHDN) provides a platform for professionals and people affected by HD to facilitate working together throughout Europe. It facilitates natural history studies and interventional trials that meet high clinical standards (Good Clinical Practice), thereby helping on the road towards effective treatments for HD. It is a true network in that all participants involved can take a lead and propose, conduct, and publish studies. The EHDN is organized into study sites, working groups, coordination centres organized according to language, an Executive Committee, and a Scientific and Bioethics Advisory Committee. The EHDN provides an infrastructure for large-scale HD clinical trials, central coordination including an information technology core facility, a forum for close cooperation of basic scientists and clinicians, and native language support for study sites by language group coordinators.
The nascent Latin American network, Red Latino-americana de Huntington (RLAH), was established in February 2010 by clinicians and HD-affected families. Its major aim is to promote and aid Huntington’s disease research in Latin Americathrough participation in Enroll-HD, as well as to serve as a platform for clinical trials. To date, 13 clinical sites in Argentina, Brazil, Chile Ecuador, Peruand Venezuelahave joined the network.
COHORT was a coordinated effort by approximately 42 Huntington Study Group (HSG) research centres in theUnited States,Canada, andAustraliato collect information from individuals who are affected by HD and those who are part of an HD family. The HSG collected this information in order to learn more about HD, potential treatments, and to plan future research studies of experimental drugs aimed at postponing the onset or slowing the progression of HD. COHORT enrolled 1500 participants.
Enroll-HD is a worldwide observational study for Huntington’s disease families, covering from North and South America to Europeand the Asia Pacific region. The primary objective of Enroll-HD is to improve the understanding of the dynamic phenotypic spectrum and the disease mechanisms of HD by: 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; collecting data and biologic samples to identify genetic and environmental factors that affect HD phenotype and disease progression; and promoting interrogatory studies that may provide clues to the pathogenesis of HD. This open-ended study requires patients to attend one visit each year. Enroll-HD is a continuation and extension of the established observational studies REGISTRY (Europe) and COHORT (North America/Australia), and builds on their many strengths and successes. With the full support of the HD community - clinicians, patients, families, researchers, and advocates – Enroll-HD expects to greatly enhance the available clinical information on Huntington’s disease and create opportunities for future research.
The REGISTRY V3 is a multi-centre, multi-national observational study with no experimental treatment. It is one of the largest research studies for Huntington’s disease in Europe, collecting precious clinical data and biological samples to help comprehend why and when the symptoms appear in HD and to identify new therapies. The Registry aims to include the largest possible number of people affected by HD.
Track-On HD involves 240 participants over 2 years from 4 international sites - Leiden (The Netherlands), London (UK), Paris (France), Vancouver (Canada) - and was born out of the success of its forerunner, TRACK-HD, with the aim of extending the results of that study to HD gene-carriers that have not yet developed disease symptoms (pre-manifest). Pre-manifest participants show little or no overt sign of disease, so more sensitive measures are required that can capture these very subtle changes that are taking place as the disease progresses. Once specific markers of pre-manifest disease stages are identified then a clear roadmap can be designed to test candidate therapies targeted at stages before symptom onset. Since the biological changes caused by the HD gene mutation are complex and act across different levels of physiology and behaviour, Track-On HD, like its predecessor TRACK-HD, includes a number of different measures and methods to characterize and map disease progression.