By Jamie Level, Eileen Neacy, and
Christina Sampaio, MD PhD
The first ever Enroll-HD Congress was held from May 20-22, 2018 in Quebec City. Enroll-HD is a worldwide observational study for HD families that monitors how the disease appears and changes over time in different people. People from all over the world—Enroll-HD principal investigators and site staff, the Enroll-HD study team, industrial colleagues, Huntington disease (HD) researchers, and patient advocacy colleagues—participated in the Congress where everyone had the opportunity to connect, learn, and share ideas and experiences among the global Enroll-HD clinical community.
Enroll-HD is evolving to meet the research challenges of 2025 and, over the course of the Congress, attendees listened to presentations describing modifications and innovative initiatives added to the Enroll-HD platform and observational study, advances in HD clinical research, and new scientific findings in HD pathophysiology.
Clinical Research Enters New Phase
HD clinical research is entering a new and exciting phase, and not since the discovery of the HD gene 25 years ago has there been such hope in our community. Antisense oligonucleotides that aim to lower huntingtin are now in full clinical development and were described by the keynote and featured speakers, Rachelle Doody from Roche and Blair Leavitt from the University of British Columbia. Other potential disease-modifying interventions are also fast approaching the clinical stage, and the extended HD community—families, clinicians, researchers—has all contributed to reaching this point. However, the takeaway message from the Congress is that there remains much more to do, and the Enroll-HD platform is primed to serve the HD community for most of its research needs.
The big data era brings with it new data analysis and statistical methodologies that can reveal patterns, associations, and other information from large datasets in a way that was not possible before. Enroll-HD—along with its predecessors, Registry and COHORT, as well as other observational studies such as PREDICT, Track-HD/Track-On, and ImageHD—contributes to the current wealth of HD clinical data that are available to researchers. These datasets have been integral to the development of descriptive and predictive disease models, as well as to fundamental genome-wide association studies that have identified modifier genes, and several of these were presented at the Congress.
The C-Path Establishes HD Consortium
The Critical Path Institute (C-Path), a nonprofit organization experienced in building precompetitive consortia that work with regulatory authorities to map efficient pathways to approval of new therapeutics, has recently established such a consortium for HD. The first product of the Huntington Disease Regulatory Sciences Consortium is the Clinical Data Interchange Standards Consortium (CDISC) data standards for HD. These standards are required for regulatory submissions and will maximize the value of the information contributed by research participants by streamlining clinical research and facilitating data sharing and comparison. The critical role that data sharing can play in the advancement of clinical science was presented and discussed during the Congress, and the full implementation of these CDISC standards should be an immediate priority for the HD research community. A well-attended half-day workshop on how to utilize the datasets and statistical methods for HD research followed the Congress, and it is imperative that the HD research community join together to make all HD clinical datasets widely available, including invaluable interventional trial datasets.
HD Resource Fair
The Congress resource fair was an opportunity to learn about these datasets and other resources, including the extensive collection of HD biosamples now available for researchers to test new ideas. This substantial base of over a million aliquots of biomaterial is expanding with the collection of new sample types such as cerebrospinal fluid and plasma from HDClarity, fibroblasts from the Multi-Tissue Study, plasma from Enroll-HD, and sperm from the Origin-HD study that will soon begin. Combined with deep phenotypic and morphometric data, these biosamples are a rich and easily accessible source of material for exploration that researchers are encouraged to access (https://www.enroll-hd.org/for-researchers/access-data/).
Enroll-HD is a unique clinical research infrastructure that has now reached maturity. It is being used to develop the tools that HD clinical research urgently needs—drug development biomarkers and more sensitive clinical assessments tailored to different stages of HD. Now, more than ever, the HD research community must work together and use our resources effectively across many fronts to deliver key tools that will expedite the development of therapeutics for HD.