STEPPING INTO THE FUTURE OF HD RESEARCH A lot has happened since the last issue of Enroll! Le Chateau Frontenac in Quebec City, the conferencecenter and hotel for the Enroll-HD Congress in May2018, was lit up blue in honor of HD Awareness Month It’s good to be back! This latest issue of Enroll! lands at an especially promising time in HD research. Everywhere you look, from the lab bench to the clinical exam room, the excitement about the latest scientific advances is palpable. With promising drug candidates either approaching or currently in clinical trials, there has never been a more important time to become a part of research. Our Enroll-HD community continues to grow—today, we have more than 20,000 participants from 19 different nations located across 174 clinical sites on four continents. Every Enroll-HD participant and clinical staff member has been instrumental in reaching these impressive milestones. But there also remains much more for us to accomplish. Together, this vibrant network of participants, their families, clinicians, site staff, and researchers must continue to expand and evolve to meet the research challenges of the next decade. Enroll-HD is now providing a wealth of clinical data to researchers, and as these datasets continue to grow they will allow us to better describe HD, further understand the genetics that contribute to disease progression, and offer new ideas about how to develop effective treatments. Scientific discovery is accelerated when people collaborate and share knowledge. In May 2018 clinicians and researchers from the worldwide Enroll-HD network gathered for the first ever Enroll-HD Congress in Quebec City, Canada. It was a unique opportunity to learn, connect, and express ideas that will propel HD research forward. Some of the highlights discussed included new initiatives and studies for the Enroll-HD platform, advances in HD research, and clinical findings that have provided novel insights into how HD develops, affects the body, and manifests in patients. Noteworthy accomplishments Since our last issue researchers have made remarkable progress in drug development. Medications known as antisense oligonucleotides that can lower levels of the huntingtin protein that causes HD are now in phase III clinical trial—the last step of testing before regulatory authorities approve a medication—to evaluate whether or not the lowered amount of huntingtin translates into clinical benefit. Other interventions of various types that aim to lower huntingtin protein are also rapidly approaching clinical trials (see the Postcard from Palm Springs video on the www.enroll-hd.org homepage for further details). To accelerate the development and approval of new drugs, the Huntington’s Disease Regulatory Science Consortium (HD-RSC) has been established by CHDI in collaboration with the Critical Path Institute, a nonprofit organization that works with drug developers and regulatory authorities like the Food & Drug Administration (FDA) and the European Medicines Agency (EMA). Made up of pharmaceutical and biotechnology industry partners, academic institutions, government agencies, patient-advocacy organizations, and technology industry partners, the HD-RSC works in coordination with regulatory officials to plan the approval process for new drugs. Progress is already underway. The HD-RSC has established data standards that are required when new drugs are submitted to regulatory agencies for approval. These data standards will maximize and streamline how the information contributed by Enroll-HD participants is gathered, shared, and compared. With these standards in place, the Enroll-HD database will become an even more powerful resource for researchers. Expanding and sharing our database During the Congress, researchers had the opportunity to learn about the extensive datasets and associated biosample resources available to test new ideas and design experiments. More than 150 researchers around the globe are now using the Enroll-HD database, which has also been used to help design 10 platform studies and five clinical trials, with more currently being planned. With promising drug candidates either approaching or currently in clinical trials, there has never been a more important time to become a part of research Enroll-HD now has a collection of over a million HD biosamples available; these include DNA and blood cells from Enroll-HD, cerebrospinal fluid and plasma from HDClarity, and will soon extend to plasma from Enroll-HD and sperm from the Origin-HD study. Some of the most notable platform studies are looking to develop two vital tools: biomarkers for drug development that measure a disease-related process going on in the body, and clinical assessment tools tailored to different stages of HD. The future of HD research To accelerate the pace of discoveries it is imperative that data continues to be shared openly and made available to the HD research community. In November 2017 Enroll- HD introduced a new strategy to recruit premanifest participants as early as possible (see article page 3), even if they have not been tested for the gene. Studying behavior and collecting samples from people before disease onset will enable the development of better biomarkers and detailed characterization of the earliest stages of HD. As new drugs are developed, it will be essential to have insight into this critical window before disease begins. It will also prepare for a future where premanifest people can be treated early so that they only develop symptoms late in life, or not at all. We hope you enjoy this issue of Enroll! After you learn about the new premanifest recruitment strategy, meet some of the faces of HD who are advocating on the frontlines. Then see some of the ways leading HD researchers use participant data and take an inside look at some of the research studies that use the Enroll-HD platform. Working together, the HD community is making a difference for patients and families.