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HDSA RESEARCH REPORT Moving Forward and Staying Connected Through Challenging Times Huntington’s Disease Society of America Huntington’s Disease Society of America 505 Eighth Avenue, Suite 902 New York, NY 10018 www.HDSA.org A Year to Forget Cannot 1.800.345.HDSA [email protected] Stop Our Progress Dear Friends, dose. Novartis announced plans to launch a Phase 2 trial to investigate an orally administered drug to lower The COVID-19 pandemic has huntingtin. Triplet Therapeutics began (and fully THE MARKER affected all aspects of our society. THE 2020 HDSA RESEARCH REPORT recruited) Shield-HD to better understand how the Over a million lives have been lost, CAG repeats in the huntingtin gene expand to prepare millions more jobs are gone and them to test a drug that could interfere with this CONTENTS countless businesses have been process and Azevan reported clinical trial data shuttered. The research community Fellowships 3 suggesting their drug, SRX-246 may improve was not immune to the consequences irritability and aggression in HD patients. HD Trialfinder 7 of this virus. HD laboratories around the world locked their doors and recruitment to clinical trials in many While 2020 will undoubtedly go down in history as Clinical Trial Updates 9 cases was halted to curb the spread of the virus. one of the most challenging years ever, I will remember it as a year of unprecedented expansion of our HD drug HD Research Hot Topic: CRISPR/Cas9 — The pandemic forced HDSA to cancel its in-person pipeline. An expansion based on solid science from A Tool for Precise Genome Editing 14 Annual Convention for the first time in our history. observations in humans. So, while we anxiously await However, cancelling Convention altogether was never HDSA Research Communications 15 results from the current huntingtin lowering trials like an option, so, the HD community did what it always Generation-HD1 and Precision-HD1/2, I am excited HD Research Conferences 16 does… adapt and persevere. We came together quickly and more hopeful than ever by the depth and diversity to convert our New Orleans Convention into a virtual of our clinical trial bench. HDSA Centers of Excellence 18 event that safely reached more than 1500 people in over 90 countries. It was here that families got first- I hope that you enjoy reading about our expanding drug HDSA’s Scientific Advisory Board 20 hand updates from scientists and clinicians from pipeline in this year’s The Marker and here is to a safe around the globe on our collective progress since and happier 2021 with continued progress towards a Head Writer: Leora Fox, PhD we last met in Boston. world free of HD! © 2020 Huntington’s Disease Society of America. Despite the setbacks 2020 presented, this year marked All rights reserved. several notable events in the history of HD research. uniQure dosed the very first HD patient in the US with an experimental gene therapy that could permanently George Yohrling, PhD lower levels of the huntingtin protein with just one Chief Scientific Officer & Chief Mission Officer, HDSA THE MARKER Huntington’s Disease Society of America 1 2020 Research Report 2020 Human Biology Project Fellowships In October of 2020, HDSA awarded four grants disease science in the human condition. Applicants under the Society’s largest research initiative, the worldwide proposed projects addressing HD through HDSA Huntington’s Disease Human Biology Project. small clinical studies or donated human samples. These grants, totaling $523,000, represent HDSA’s This year’s winners hail from Australia, Canada, patient-centric research focus which brings basic and Germany, and the United States. clinical researchers together to facilitate Huntington’s Simon Laganiere, MD Bjoern von Einem, PhD Yifat Glikmann- Melanie Alpaugh, PhD Beth Israel Deaconess Hospital University of Ulm Johnston, PhD Université Laval Monash University Dr. Laganiere will use Dr. von Einem’s project is Dr. Alpaugh aims to identify innovative imaging focused on improving upon Dr. Glikmann-Johnston factors in the blood, including techniques to study how the technology to monitor will carry out a large study a protein called tau, that brain networks interact in the effectiveness of huntingtin- to understand the key could be used to track presymptomatic individuals lowering ASO drugs that are differences in gut bacteria cognitive symptoms of HD. during challenging cognitive currently in clinical trials. between people with and A reliable and noninvasive tasks. This type of mental The goal is to noninvasively without the HD gene. This tool to predict which stress test can show HD measure huntingtin in the foundational work will serve individuals are likely to related brain changes earlier spinal fluid, by sampling tiny to determine whether there develop cognitive deficits than they would otherwise bubbles called exosomes. is a relationship between the would have important appear. If successful, results This work will help guide microbiota in our intestines, implications for clinical from this study will help the development of potential and mood and cognition in trials as well as symptom determine the optimal disease-modifying treatments people with HD. The gut management. timing for eventual disease for HD. may be an excellent target modifying treatments. for drug development and dietary interventions. THE MARKER THE MARKER 2 Huntington’s Disease Society of America Huntington’s Disease Society of America 3 2020 Research Report 2020 Research Report 2020 Donald A. King Summer Research Fellowships In May 2020, five exceptional In order to further meaningful each year and are reviewed After rigorous review by the Funding for this year’s undergraduate students were discoveries about Huntington’s by HDSA’s Scientific Advisory HDSA’s Scientific Advisory Don King Fellows was made awarded HDSA’s Donald A. King disease and ensure that bright Board. Board, five young scientists, possible, in part, by a generous gift Summer Research Fellowships. young scientists are steered the most in the history of from Hal and Isabelle Pilskaln. This year’s applicants were These awards are named in towards the field, this program this program, were awarded evaluated by the quality of their Funding HD research has been honor of Donald King, who supports undergraduates who 2020 Donald A. King Summer personal academic achievements, a life-long passion for the Pilskalns served as HDSA Board Chairman have committed their summers Research Fellowships. Due to mentoring plan, experimental and HDSA is indebted to them from 1999 to 2003 and worked to training in an HD research this year’s unusual circumstances, design, and the feasibility of for their support. tirelessly to advocate for HD lab. Applications are accepted these projects were extended achieving their scientific goals. families until his death in 2004. between December and March throughout 2020. Sophia Friedman Amber Keith Lav Patel Tasneem Sadok Kadambari Vyas Wellesley College University of California at Irvine Ohio State University University of California at Los Angeles University of Central Florida Sophia is completing her project Amber worked with Sarah Lav is doing HD research in the Tasneem is working under the Kadambari was mentored by at the Massachusetts Institute of Hernandez, PhD, a 2017 HDSA laboratory of Richard Fishel, PhD, guidance of Lindsay DeBiase, PhD, former HDSA Human Biology Fellow Technology with David Housman, Berman-Topper Career Development where he aims to visualize DNA to study how changes in energy Dr. Amber Southwell and studied PhD, exploring genes known to alter Fellowship recipient, in the repair proteins that affect the production affect the brain’s support aggression in mouse models of HD. the onset of HD symptoms. laboratory of Dr. Leslie Thompson, expansion of CAG repeats. cells in areas vulnerable to HD. to develop a model of the blood-brain barrier derived from human cells. THE MARKER THE MARKER THE MARKER 4 Huntington’s Disease Society of America Huntington’s DiseaseHuntington’s Society of Disease America Society 5of America 5 2020 Research Report 2020 Research Report2020 Research Report 2020 Berman-Topper Family HD Trialfinder HD Career Development Fellowship As part of HDSA’s commitment to developing of Massachusetts Medical School had been granted In 2015, to facilitate participation in clinical trials Trialfinder listing stays up-to-date with studies that the next generation of passionate and innovative this distinguished award for 2020. for both families and researchers, HDSA created need participants. Anyone can visit the website to Huntington’s disease scientists, the Berman-Topper HD Trialfinder, a clinical trial matching service. It read about ongoing studies, and by creating a profile Dr. Gholamalipour’s project will attempt to reverse Family HD Career Development Fellowships provide is a way for individuals with Huntington’s disease, for yourself, a loved one, or a patient, users can find the CAG repeat expansion sequence in the mutant up to $80,000 of funding per year for three years to caregivers, healthy volunteers, out which nearby studies they are eligible huntingtin gene back to the normal range (less than young scientists and clinicians who desire to make and physicians to connect with for, and locate contact information to get 36 CAG repeats) in cellular and animal HD models HD part of their long-term career plan. These current research studies. involved directly. This year we saw the using the CRISPR-Cas9 nickase genome-editing tool. prestigious awards are made possible due to the HD Trialfinder includes an easy- number of HD Trialfinder users grow to generosity of the Berman and Topper families. Upon hearing the announcement of Yasaman’s to-use website and free call center staffed over 7,500. They have undoubtedly contributed selection, Michael Berman said, “Dr. Gholamalipour by trained HD clinical trial navigators. to the speedy US recruitment of three huntingtin- HDSA received applications from researchers joins a terrific group of young scientists who have lowering trials.
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