HSG 2017 Abstract Lay Summaries

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1. Current Challenges and Future Opportunities: The HD Care Improvement Project

Karen Anderson1, Jack Griffin2, Stevan Ramirez3, Joni Steinman4, Al Kinel4, Shari Kinel3
1Georgetown University
2Griffin Foundation
3Huntington Study Group
4Strategic Interests
Lay Summary: This project looks at how to improve clinical care, services, and research for Huntington’s disease (HD). Detailed interviews were done with a number of key players, including: care providers and social workers, basic and clinical researchers, leadership of HD organizations, leadership of non-HD organizations (e.g., biopharma). Current challenges include lack of cooperation between various HD organizations.  Strategies for future collaboration are described.

2. Improving Care for People with Huntington’s Disease (HD) and Their Families: The HD Care Improvement Project

Karen Anderson1, Jack Griffin2, Stevan Ramirez3, Joni Steinman4, Al Kinel4, Shari Kinel3
1Georgetown University, Washington, DC, USA
2Griffin Foundation, Potomac, MD, USA
3Huntington Study Group, Rochester, NY, USA
4Strategic Interests, LLC, Rochester, NY, USA

Lay Summary: This abstract outlines our recent efforts to identify gaps in clinical care provided to people with HD and their families. A survey was developed with help from a Huntington Study Group HD focus group and the consulting firm PriceWaterhouseCoopers. Results showed that many people with HD do not receive care from HD specialists, but those who do found specialty care to be very helpful. A need for more HD information and HD education in the medical community was identified. Online resources may help to fill some of these gaps in knowledge and care.

3. Measurement of Huntington’s Irritability and Aggression in the Azevan Pharmaceuticals-NeuroNext STAIR Study

Karen Anderson1, Steve Hersch2,4, Jeffrey Long3, Merit Cudkowicz4, Christopher Coffey5, Jon Yankey5, Michele Costigan5, Sabrina Raulerson4, Samantha Berg4, Robin Conwit6, Codrin Lungu6, Michael Brownstein7, Neal Simon7
1Georgetown University School of Medicine, Washington, DC, USA
2Voyager Therapeutics Inc., Cambridge, MA, USA
3Department of Psychiatry and Department of Biostatistics, University of Iowa, IA, USA
4Massachusetts General Hospital, Boston, MA, USA
5Department of Biostatistics, University of Iowa, Iowa City, IA, USA
6Robin Conwit, National Institute of Neurological Disorders and Stroke Bethesda, MD, USA
7Michael Brownstein: Azevan Pharmaceuticals, Inc., Bethlehem, PA, USA

Lay Summary: Irritability and aggression are very common symptoms in Huntington’s disease (HD); they contribute greatly to the burden of disease experienced by patients, their family members, and other caregivers. There are currently no approved drugs to treat these symptoms in HD. This is a clinical trial of a new medication that may help to treat irritability and aggression.  Thus far, 69 people with HD are in the study. We are looking at how well various patient and caregiver scales work to measure irritability and aggression in this ongoing study. This is important because to show whether the study medication works, we need to have good measurement tools that reflect the kind of symptoms seen in HD.

4. Prenatal Genetic Testing for Huntington’s Disease: Ethical Considerations

Setareh Ashtiani1, Jasmine Doonanco2, Oksana Suchowersky1,2
1Department of Medicine (Neurology), University of Alberta, Canada
2Department of Medical Genetics, University of Alberta, Canada

Lay Summary: We present the case of a 30-year-old woman who became pregnant shortly after completing predictive testing for Huntington’s disease, where she learned she carries the gene mutation. She requested to have the genetic test for her fetus, although she wanted to continue the pregnancy regardless of the result. She expressed that knowing the genetic result for this child would help her plan her future pregnancies. Ethical and counseling issues are reviewed to explain that in this situation, testing the fetus is the same as testing an asymptomatic child, and therefore testing is not appropriate.

5. Special Considerations in Cases with an Absence of Documented Family History of Huntington’s Disease

Tanya Bardakjian, Kaylee Naczi, Rachel Paul, Pedro Gonzalez-Alegre
University of Pennsylvania, Philadelphia, PA, USA

Lay Summary: HD is an autosomal dominant condition. The absence of a documented family history of HD specifically is often misleading to non-experienced clinicians.  Special considerations should be made when evaluating and diagnosing individuals with HD when there is an absence of a well-documented family history.

6. Understanding the Educational Needs of Neurologists Who Manage Patients with Huntington’s Disease: A Study Analyzing Both Clinician and Patient Perspectives

Justin Barnes, Lee Whitworth, Brandon Coleman, Sharon Hwang, Gregory Salinas
CE Outcomes, Birmingham, AL, USA

Lay Summary: This is the first assessment of the approaches neurologists use to diagnose and manage patients with HD. Comparing the observed practice patterns to HDSA guideline recommendations and clinical trial evidence identified aspects of neurologist practice that should be targeted with future educational programming. An assessment of patient and caregiver perspectives, educational needs, and barriers to care also uncovered differences in treatment priority between patients and their caregivers.

7. Safety and Tolerability of SRX246 in Irritable/Aggressive Subjects with Huntington’s Disease (STAIR): A Phase II Exploratory Clinical Trial

Sabrina Raulerson1, Samantha Berg1, Michele Costigan2, Steve Hersch3, Karen Anderson4, Jeffrey Long2, Chris Coffey2, Jon Yankey2, Merit Cudkowicz1, Robin Conwit5, Codrin Lungu5, Michael Brownstein6, Neal Simon6
1Massachusetts General Hospital, Boston, MA, USA
2Biostatistics, University of Iowa, Iowa City, IA, USA
3Voyager Therapeutics Inc., Cambridge, MA and Mass. Gen. Hosp./Harvard Med. Sch., Charlestown, MA, USA
4Georgetown University School of Medicine, Washington, DC, USA
5National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
6Michael Brownstein: Azevan Pharmaceuticals, Inc., Bethlehem, PA, USA

Lay Summary: In HD, psychiatric symptoms, including irritability and aggression, adversely impact daily life and often result in institutionalization. New medicines to treat these neuropsychiatric symptoms are needed because available drugs are minimally effective and several have significant side effects. In the current clinical trial (NCT02507284), SRX246, a novel, first-in-class vasopressin 1a (V1a) receptor antagonist that shows promise as a treatment for irritability and aggression, is being tested in HD patients to assess tolerability, generate additional safety data, and explore scales that measure these symptoms for use in future clinical trials.

8. Neurofilament Light Chain in Blood as a Predictor of Onset, Progression, and Brain Atrophy in Huntington’s Disease: A Longitudinal Cohort Analysis

Lauren M. Byrne1, Filipe B. Rodrigues1, Kaj Blennow2,3, Alexandra Durr6, Blair R. Leavitt4, Raymund A.C. Roos5, Rachael I. Scahill1, Sarah J. Tabrizi1, Henrik Zetterberg1,2,3, Douglas Langbehn7, Edward J. Wild1
1UCL Institute of Neurology, London, UK
2Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, MöIndal, Sweden
3Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, MöIndal, Sweden
4Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada
5Leiden University, Netherlands
6Institut du Cerveau et de la Moelle Épinière (ICM), Sorbonne Université, Paris, France
7University of Iowa, Iowa City, IA, USA

Lay Summary: These results on neurofilament light protein give evidence for the first blood test that can predict HD progression, including disease onset and the rate of brain atrophy. It has the potential of facilitating therapeutic development by helping decide whether a drug is slowing the rate of damage to brain cells in HD.

9. Enroll-HD: A Clinical Research Platform for HD

Selene Capodarca1, Olivia Handley1, Jamie Levey1,2, Tim McLean1, Bernhard Landwehrmeyer3, Cristina Sampaio2 (on behalf of the Enroll-HD Steering Committee)
1EHDN, University of Ulm, Germany
2CHDI Management/Foundation, Inc., Princeton, NJ, USA
3University of Ulm, Germany

Lay Summary: Enroll-HD is a clinical research platform that includes an observational study on HD. Eligible participants include individuals who are gene expansion carriers, gene negative, individuals with unknown genotype, and controls. Data are collected annually on motor, cognitive, and behavioral symptoms, releasing coded data to researchers periodically.

10. Effects of Physical Therapy Home Program Plus Community-Based Exercise Classes for a Person with Early-Stage Huntington’s Disease: A Case Report

Adrianna Carey
Good Shepherd Penn Partners/Penn Therapy & Fitness, HDSA Center of Excellence, University of Pennsylvania, USA

Lay Summary: This case study describes changes in falls risk and self-reported falls in a person with early-stage HD after a 14-month period using daily practice of PT home exercise program in addition to community-based exercise classes. Although the person’s fall risk increased after 14 months, the person reported no falls within the same period.

11. Exploring the Transcriptional Consequences of Long-Term Huntingtin Lowering In Vivo

Sydney R. Coffey 1, Jeffrey P. Cantle 1, Robert M. Bragg 1, Samuel R. W. Legg 1, Fiona Kinsella 1, Kylee Haagenson 1, Will Hovander 1, Miguel Sena-Esteves 2, David S. Howland3, Jeffrey B. Carroll 1
Behavioral Neuroscience Program, Department of Psychology, Western Washington University, Bellingham, WA, USA
Department of Neurology, Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA
CHDI Foundation, Princeton, NJ, USA

No Lay Summary

12. FightHD Neuroplasticity-Based Treatment for Huntington’s Disease

Melanie Cheung1, Leo Sugrue2, Elizabeth Tong2, Jo Dysart3, Greg Finucane4, Lynette Tippett5, Margaret Dudley5, Soweeta Fort-D’Ath1, Richard Faull1, Mike Dragunow6, Mike Merzenich7.
1Department of Anatomy and Medical Imaging, University of Auckland, NZ
2Department of Radiology and Biomedical Imaging, University of California San Francisco, USA
3Liaison Psychiatry, Auckland District Health Board, NZ
4Liaison Psychiatry, Waitemata District Health Board, NZ
5School of Psychology, University of Auckland, NZ

6Department of Pharmacology, University of Auckland, NZ
7Posit Science, USA

Lay Summary: Our research team has developed a novel treatment for Huntington’s disease (HD) called FightHD. The treatment harnesses neuroplasticity (the brain’s natural ability to change in response to the input it receives) to fight HD progression. It’s thought that brain cells begin to die when they lose their connections to other brain cells. We want to know if we can stop the cells from becoming disconnected, can we slow down the brain cell death that causes HD? We’ve also designed FightHD to strengthen brain processes, which are damaged early in HD.

13. Review of Neuropsychiatry in a Huntington’s Disease Clinic

Elvina May-Yin Chu1,2, Caitlin Hartney3
1The National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, England
2St Andrew’s Healthcare, Northampton, England
3Kings College London, London, England    

Lay Summary: Typically there is no clinical input from psychiatry available in neurology clinics. This review provides objective evidence of how frequently psychiatric symptoms present in HD and also demonstrates that those with more prominent psychiatric presentations benefit from assessment and treatment by a consultant neuropsychiatrist. This is important to the HD community so appropriate clinical care can be sought.

14. Investigating the Clinical Predictors of Depression in Huntington’s Disease: An Enroll-HD Database Study

Gabriela Delevati Colpo, Natalia Pessoa Rocha, Erin Furr Stimming, Antonio Teixeira
University of Texas Health Science Center at Houston, Houston, TX, USA

Lay Summary: The presence of depression is a burden for both individuals with HD and their caregivers. In addition, depression is an important predictor of suicidal behavior. In this context, this study helps to identify and characterize depression in individuals with HD and to treat the patients with more effectiveness, improving their quality of life and the quality of life of their caregivers. Also, to identify depression at an early stage helps to avoid severe consequences, such as suicidality.

15. Optimization of Chemically Modified siRNA for Allele-Specific Targeting of Human Huntingtin

Faith Conroy, Julia Alterman, Matthew Hassler, Dimas Echeverria, Neil Aronin, Edith Pfister, Anastasia Khvorova
University of Massachusetts Medical School, Worcester, MA, USA

Lay Summary: Chemically modified siRNAs (hsiRNAs) have allowed us to achieve full silencing of the huntingtin protein via RNAi; however, selective silencing of only the mutant allele has been difficult to perfect. We have established a method for optimizing allelic discrimination, utilizing hsiRNAs, with unique chemical modification patterns, that target a patient-specific heterozygous SNP in the HTT mRNA.

16. Handwriting Movement Abnormalities as an Early Biomarker of Transition to Manifest Huntington’s Disease

Sungmee Park1, Jody Corey-Bloom1, Ajay Nathan1, Chase Snell1, Michael Caligiuri2
1Department of Neurology, University of California, San Diego, La Jolla, CA, USA
2Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA

Lay Summary: We examined movement abnormalities in handwriting to see if they might be a good marker of HD onset. We found that, in fact, they were, and were present quite early in the transition period to manifest HD.

17. Salivary Biomarkers for Huntington’s Disease

Jody Corey-Bloom1, Sungmee Park1, Ameera Haque1, Aeri Kim1, Ajay Nathan1, Douglas Granger2, Steven Granger3, Elizabeth Thomas4
1Department of Neurosciences, University of California San Diego, La Jolla, CA, USA
2Institute for Interdisciplinary Salivary Bioscience Research, UCI, Irvine, CA, USA
3Salimetrics, Carlsbad, CA, USA
4Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA, USA

Lay Summary: The objective of our study was to examine the potential for saliva to serve as an accessible biomarker for HD. We found that it is not only possible to measure huntington protein in saliva, but also other proteins that may be important indicators of disease onset and progression.

18. The Impact of Living with Huntington’s Disease on Family Caregivers and Those at Risk for the Disease

Amita Risbud1, Sungmee Park2, Ajay Nathan2; Jody Corey-Bloom2
1Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA
2University of California, San Diego, La Jolla, CA, USA

Lay Summary: We studied behavioral symptoms in HD caregivers and individuals at risk for HD. We found that individuals caring for HD patients and those at risk for HD, who were gene positive or did not know their genotype, had significantly more behavioral issues such as anxiety and depression.

19. Lumateperone (ITI-007): A Novel Approach for the Treatment of Multiple Neuropsychiatric and Neurologic Diseases

Sharon Mates, K. Vanover, C. O’Gorman, J. Saillard, M. Weingart, G. Snyder, J.P. Hendrick, P. Li, L.P. Wennogle, R.E. Davis
Intra-Cellular Therapies, Inc., New York, NY, USA

Lay Summary: Lumaterperone is a new a drug being developed to treat the many symptoms that accompany psychiatric and neurologic diseases. It may be useful in reducing depression, anxiety, apathy, and irritability in patients with HD.

20. Longitudinal Analysis of Mutant Allele-Specific Silencing in the YAC128xNSG Mouse Using Transcription Activator-Like Effectors

Peter Deng1, Julian Halmai2, Grace Tharmarajah3, Ivette Sandoval4, Fredric Manfreddson4, David Segal1, Jan Nolta2, Kyle Fink5
1Genome Center, MIND Institute, and Biochemistry and Molecular Medicine, University of California, Davis, CA, USA
2Stem Cell Program and Institute for Regenerative Cures, University of California Davis Health Systems, Sacramento, CA, USA
3Precision Nanosystems Inc, Vancouver, BC, Canada
4Translational Science & Molecular Medicine, Michigan State University, Grand Rapids, MI, USA
5Department of Neurology, University of California Davis Health Systems, Sacramento, CA, USA

Lay Summary: The importance of a therapeutic that selectively silences the mutant Huntingtin gene is of vital importance given the necessity of healthy Huntingtin for neuronal functioning. Our group has developed a specialized DNA-binding protein that selectively targets and silences the mutant Huntingtin gene in patient cells and animal models of HD. Our current work presents the potential of this therapeutic to improve motor deficits in an animal model of HD.

21. Latent Toxoplasma gondii Infection Promotes Neurodegeneration and Increases Soluble Mutant Huntingtin Levels in a Mouse Model of Huntington’s Disease

D.W. Donley1,2, T. Jenkins3, S. Agrawal2, M.J. Realing4, V. Chopra5, S. Hersch5, J.G. Gigley6, J.H. Fox1,2
1Graduate Neuroscience Program, University of Wyoming, Laramie, WY, USA
2Department of Veterinary Sciences, University of Wyoming, Laramie, WY, USA
3WWAMI, College of Health Sciences, University of Wyoming, WY, USA
4Department of Microbiology, University of Wyoming, Laramie, WY, USA
5MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA, USA
6Department of Molecular Biology, University of Wyoming, Laramie, WY, USA

Lay Summary: While HD is genetic, the environment plays a role in both onset and progression of the disease. Our research indicates the potentiation of HD by chronic infection and illustrates the contribution of environmental factors to HD progression.

22. Clinical Development of VX15 Anti-Semaphorin 4D Antibody as a Potential Treatment for Huntington’s Disease

Zauderer1, J. Leonard1, T. Fisher1, E. Evans1, D. Fisher1, L. Balch1, E. Smith1, A. Feigin2
1Vaccinex, Inc., Rochester, NY, USA
2For the Huntington Study Group SIGNAL investigators and coordinators, and the University of Rochester Clinical Trials Coordination Center, Rochester, NY, USA 

Lay Summary: The SIGNAL trial of Vaccinex’s anti-SEMA4D antibody in prodromal and early manifest HD has raised no concerning safety signals, and recruitment and retention have been excellent. Biomarker imaging results of the first part of the trial are encouraging. These results have informed the design of the second part of the trial, which continues to actively enroll late prodromal and early manifest patients.

24. A Multidisciplinary HD Clinic’s Initial Experience with the New Canadian Legislation Allowing Medical Assistance in Dying

C.A. Gibbons1,2, W.L.A. Fung1,3, B. Henry1,4, S. Esmail1,5
1North York General Hospital, North York, Ontario, Canada 
2Department of Molecular Genetics, University of Toronto, Toronto, Canada
3Department of Psychiatry, University of Toronto, Toronto, Canada
4Department of Family and Community Medicine, University of Toronto, Toronto, Canada
5Department of Medicine, University of Toronto, Toronto, Canada

Lay Summary: Health care providers are trying to understand the new Canadian legislation allowing medical assistance in dying (MAID) and how it applies to patients with HD. The primary concern is the requestor meeting the competency requirement while having enough symptoms to be in an advanced state of decline. By sharing our experiences, we hope to educate other health care providers about ways they can support their patients who request MAID.

25. Parents’ Perspective on the Challenges of Disclosing Huntington’s Disease Information to Their At-risk Children

C.A. Gibbons1,2, W. Medved3, W. Meschino1,4, A. Lefebvre5,6, W.L.A. Fung1,6,7, J. Semotok2
1Genetics Program, North York General Hospital, North York, Ontario, Canada
2Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
3Canadian Institute for Health Information, Toronto, Ontario, Canada
4Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
5Hospital for Sick Children, Toronto, Ontario, Canada
6Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
7Department of Psychiatry, North York General Hospital, North York, Ontario, Canada

Lay Summary: Parents often wonder about the best way to talk to children about HD. This study explores 11 parents’ perspectives to better understand how parents plan to disclose HD information to their children. Parents can use the common themes from the study in combination with their specific circumstances to help them plan for disclosing HD information to their children.

26. Development of a Novel Patient-Reported Outcome Measure for Huntington’s Disease: The Huntington Disease Health Index (HD-HI) Study

Alistair Glidden1, Elizabeth Luebbe2, Molly Elson1, Steven Goldenthal1, E. Ray Dorsey1,2, Chad Heatwole2
1Center for Health + Technology, University of Rochester, Rochester, NY, USA
2Department of Neurology, University of Rochester, Rochester, NY, USA

Lay Summary: Patient-reported outcome measures for HD are currently lacking and vitally important. Through surveys and interviews of individuals with HD and caregivers, we have developed a new health index (HD-HI) to accurately capture the experience of those affected. Through its widespread implementation, we hope to improve the scope and efficiency of research for novel therapies and improve the lives of those with HD.

27. Predictors of Workplace Disability in a Premanifest and Manifest Huntington’s Disease Cohort

Anita M Y Goh1,2,5, Emily You1, Stephanie Perin1, Fiona J Clay3, Samantha Loi1,2, Kathryn Ellis1, Terence Chong1, David Ames1,4, Nicola Lautenschlager3
1Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, Australia
2Neuropsychiatry Unit, Melbourne Neuropsychiatry Centre, Royal Melbourne Hospital, Australia
3Department of Psychiatry, University of Melbourne, Australia
4National Aging Research Institute, Parkville, Australia
5NorthWestern Mental Health, Melbourne Health, Australia

Lay Summary: This project reports factors related to workplace disability in preHD and HD individuals, using data from the global Enroll-HD study. Employment is a defining feature of people’s lives and many people hope to maintain working for as long as they wish. We found that 1 in 8 preHD individuals, and 6 in 10 HD individuals reported experiencing workplace disability. Better physical and mental health were associated with less odds to experience workplace disability and/or to miss work. This is important to the HD community because results provide important knowledge for the development of future targeted intervention trials (e.g. health promotion activities) to support the community in employment.

28. Randomization Authorization Flow (RAF): It’s Not Just About Meeting Eligibility Criteria

Jody Goldstein, Susan Bennett, Elise Kayson
University of Rochester, Rochester, NY, USA

Lay Summary: Randomization Authorization Flow (RAF) is a robust data tool. Through RAF, the Clinical Research Team (CRT) can identify safety risks resulting in subject exclusion and/or protocol modifications. RAF reviews have resulted in cleaner data, shorter close-out timelines, and improved quality of subjects enrolled.

29. Selectivity and Biodistribution of WVE-120102, a Stereopure Allele-Specific Antisense Oligonucleotide (ASO) in Development for the Treatment of Huntington’s Disease

Serena Hung, Meena, John W. Davis II, Keith Bowman, David C.D. Butler, Foram Desai, Lankai Guo, Naoki Iwamoto, Hyun G. Jang, Maria Frank-Kamenetsky, Susovan Mohapatra, Mamoru Shimizu, Stephany Standley, Nenad Svrzikapa, Hailin Yang, Jason Zhang, Zhong Zhong, Chris Francis, Michael Panzara, Chandra Vargeese
Wave Life Sciences, Cambridge, MA, USA

Lay Summary: Wave Life Sciences is developing stereopure ASOs as potential therapies for the treatment of HD. Preclinical data demonstrating that WVE-120102 is selective for mutant vs. wild-type huntingtin will be presented. We will also review the designs of phase 1b/2a clinical trials, which were recently initiated.

30. Telemedicine Services for Huntington’s Disease: Feasibility and Initial Outcomes

Madaline B. Harrison1, Dana L. Morrissey2
1Department of Neurology, University of Virginia Health System, Charlottesville, VA, USA
2For the University of Virginia Huntington’s Disease Team

Lay Summary: Interdisciplinary specialty care for Huntington’s disease is often available only at major medical centers that cover large geographic areas, limiting access. Telemedicine brings specialty care and consultation closer to HD patients, families, and local care providers.

31. Barriers and Access to Long-Term Care: A Preliminary Investigation into Best Practices of HD Specialty Units

Hope Heller1, Stacey Barton2
1Medstar Georgetown University Hospital, Washington, DC, USA
2Washington University School of Medicine, St. Louis, MO, USA

Lay Summary: This is an initial project that will hopefully lead to further projects for the increased capacity of long-term care facilities to care for people from the HD community.

32. Gender Affects Factors Associated with Placement into Long-Term Care of Patients with Huntington’s Disease

Machteld E. Hillen1, Cheryl A. Kennedy1, Michael McCormack2, Kiran Hirapara1, Eli Kneisser1, Barbara Fadem1, Chiadikaobi Okeorji1
1Rutgers-New Jersey Medical School, Newark, NJ, USA
2Rowan University School of Osteopathic Medicine, Glassboro, NJ, USA

Lay Summary: We studied gender differences in placement to a nursing home. Our study found that placement in a nursing home differs in men and women. After diagnosis, men are sooner placed in a nursing home and this may be because they use less psychiatric medications in the community.

33. Effects of Renal Transplantation on Patient with Huntington’s Disease

Lauren Holder, Erica Sweeney, Francis Walker, Christine O’Neill
Wake Forest Baptist Medical Center, Winston-Salem, NC, USA

Lay Summary: Patients with HD can potentially experience chronic negative effects after undergoing a kidney transplant. This is important for the HD community to know, as stress on the brain, longer recovery time, and other factors should be considered before a patient with HD undergoes any major surgery, such as a kidney transplant.

35. Assessing Executive Function in Huntington’s Disease: A Comparison Between a Virtual Reality Task and Conventional Neuropsychological Tests

Filipa Júlio1,2, Alexandre Malhão2, Fábio Pedrosa2, Hélio Gonçalves2, Marco Simões2, Miguel Patrício2, Mário R. Simões1,3, Marieke van Asselen2, Miguel Castelo-Branco2,4,5, Cristina Januário2,5,6
1Faculty of Psychology and Education Sciences – University of Coimbra, Portugal
2Institute for Biomedical Imaging and Life Sciences (IBILI) – Faculty of Medicine, University of Coimbra, Portugal
3PsyAssessmentLab/Research Centre of the Cognitive and Behavioural Studies and Intervention Nucleus (CINEICC) – Faculty of Psychology and Education Sciences – University of Coimbra, Portugal
4Institute of Nuclear Sciences Applied to Health (ICNAS) – University of Coimbra, Portugal
5Faculty of Medicin, University of Coimbra, Portugal
6Coimbra University Hospital, Coimbra, Portugal

Lay Summary: There is a need to find sensitive measures that can fully grasp the real-life impact of the executive deficits often reported in HD. A more ecological cognitive assessment, with performance-based tasks, will provide crucial information about the everyday function of HD-affected individuals.

36. Physical Therapy and Exercise Interventions in Huntington’s Disease: A Mixed Methods Systematic Review

Deb Kegelmeyer1, Nora Fritz2, Anne Kloos1, Ashwini Rao3, Monica Busse4, LoriQuinn5
1The Ohio State University, Columbus, Ohio, USA
2Wayne State University, Detroit, Michigan, USA
3Columbia University Medical Center, New York City, New York, USA
4Cardiff University, Cardiff, Wales, United Kingdom
5Teacher’s College, Columbia University, New York City, New York, USA

Lay Summary: A comprehensive review of physical therapy and exercise interventions in HD was conducted. The review shows that exercise is safe, feasible, and perceived as beneficial by participants, particularly when provided in a group setting with caregiver support. Exercise improved mobility, balance, pulmonary function, and quality of life. Exercise should be standard of care for people with HD.

37. The Role of CAG Repeat Size and Parental Sex in Huntington’s Disease

Eric Keller1, Michael McCormack2, Machteld Hillen3
1Rutgers University, New Brunswick, NJ, USA
2Rowan University, Glassboro, NJ, USA
3Rutgers-NJMS, Newark, NJ, USA

Lay Summary: Our study confirmed that a larger CAG repeat size of the HD gene correlates with an earlier age of onset. We also showed that sex of the parent plays a role in inherited CAG repeat number. We are further clarifying the role of parental sex and CAG repeat size in HD.

38. Friends with Wheels: Free Transportation Pilot Helps Improve Care

Amy Chesire1, Shari Kinel2, Kristin Strazdins2
1University of Rochester, HDSA Center of Excellence, Rochester, NY, USA
2Huntington Study Group (HSG), Rochester, NY, USA

Lay Summary: The FwW pilot program is aimed at improving care for HD patients by providing free, round-trip, door-to-door, transportation to clinic visits and support groups. Overall, FwW improved 15 patients’ attendance at clinics and support groups. It allowed them to get re-connected with their HD specialists to help improve the overall treatment, care, and management of their HD. Patients greatly enjoyed the privacy, quality, and personalized driver service, in particular, compared to traditional medical transportation services. Patients and their care partners reported FwW provided them with peace of mind.

39. The Impact of Family History on the Clinical Features of Huntington’s Disease

Gabe Kringlen1,Lisa Kinsley2, Sharon Aufox3, Gerald Rouleau4, Danny Bega5
1Department of Medical Genetics at Sanford Health, Fargo, ND, USA
2Department of Neurology at Northwestern University Feinberg School of Medicine
Chicago, IL, USA
3NUgene Project, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
4Biostatistics Collaboration Center, Northwestern University Feinberg School of Medicine
Chicago, IL, USA
5Department of Neurology at Northwestern University Feinberg School of Medicine, Chicago, IL, USA       

Lay Summary: Utilizing data from the Enroll-HD registry, we found that having a positive family history of HD predicts a significantly earlier age at onset of both depression and motor symptoms, regardless of CAG repeat length, compared to affected individuals with a negative family history. We also found that those who grow up in an HD family, and those who are aware of their HD risk, have a higher prevalence of suicidal ideation, and tend to present with behavioral-psychiatric manifestations as their initial disease symptom. These findings are important to the HD community because they add to the growing list of potential modifiers of HD disease presentation.

40. Topotecan, a Topoisomerase-1 Inhibitor Retards the Disease Pathogenesis in a Mouse Model of Huntington’s Disease

Shashi Shekhar Kumar, Naman Vatsa, Vipendra Kumar, Brijesh Kumar Singh, Imran Jamal, Ankit Sharma, Nihar Ranjan Jana
Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre, Manesar, Gurgaon, Haryana India

Lay Summary: A topoisomerase-1 inhibitor, Topotecan when administered to Huntington’s disease (HD) mice, considerably improved their motor behavioral abnormalities, along with significant extension of lifespan and amelioration of progressively decreased body weight, brain weight, and striatal volume. Ultimately, we show that topotecan treatment of HD mice not only inhibits the expression of transgenic mutant huntingtin, but simultaneously induces the expression of Ube3a, an ubiquitin E3 ligase. These findings suggest that topotecan might be a potential therapeutic molecule to delay the progression of HD.

41. The UHDRS Total Motor Score in Prodromal Huntington’s Disease

Douglas Langbehn1, Bernard Ravina2, Steven Hersch2
1University of Iowa, Carver College of Medicine, Iowa City, IA, USA
2Voyager Therapeutics Inc. Cambridge, MA, USA
Lay Summary: We are still uncertain how to effectively measure prevention of clinical

Huntington’s disease onset in a trial that is short enough to be feasible. We have assessed evidence from multiple studies to demonstrate that increases in subtle motor signs are detected more reliably than subtle cognitive changes. We, nonetheless, recognize that use of motor symptoms alone may not be sufficient, and we encourage further discussion in light of the now-extensive cumulative evidence.

42. Factors That Influence Financial Decision Making in Huntington’s Disease

Sarah Mason1, Wei-Li Kuan1, Roger Barker1, Michelle Baddeley2
1John Van Geest Centre for Brain Repair, Cambridge, UK
2Institute of Choice – UniSA, North Syndey, Australia

Lay Summary: Due to the changes that have occurred in the ways in which we deal with money over recent years (Internet banking, phone sales, pin number instead of signatures, etc.) patients with dementia are at increasing risk of what is being coined “financial abuse.” Patients with HD are particularly vulnerable from this kind of abuse given their reduced capacity to manage financial information autonomously and the complex changes to their thinking capabilities. It is, therefore, imperative that we start to make moves to safeguard patients from this. The aim of this study was to identify the social, emotional, and cognitive changes that directly impact financial decision making in HD so that we can start to better understand what causes these problems before finding ways to protect patients from financial exploitation.

43. Biological Motion Perception in Huntington’s Disease

Tamara Matheis1, Lisa Muratori1,2, Ralf Reilmann1,3
1George-Huntington-Institute, Muenster, Germany
2Rehabilitation Research & Movement Performance Laboratory, Deptartments of Physical Therapy and Neurobiology, Stony Brook University, NY, USA
3Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany

No Lay Summary

44. Presence of Tau Pathology within Fetal Neural Allografts in Patients with Huntington’s and Parkinson’s Disease

Giulia Cisbani1, Alexander Maxan1, Jeffrey Kordower2, Emmanuel Planel1,3,
Thomas Freeman4,5, Francesca Cicchetti1,3
1Centre de Recherche du CHU de Quebec, Axe Neurosciences, Quebec, Canada
2Department of Neurological Sciences and Center for Brain Repair, Rush University Medical Center, Chicago, IL, USA
3Departement de Psychiatrie & Neurosciences, Université Laval, Quebec, Canada
4Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, USA
5Center of Excellence for Aging and Brain Repair, University of South Florida, Tampa, FL, USA

Lay Summary: We provide the first evidence for the presence of tau pathology in healthy tissue transplanted to Huntington’s and Parkinson’s disease patients more than a decade post-grafting. This is extremely important to the HD community as it extends the growing body of evidence that protein transfer is common to many neurodegenerative disorders, and suggests a possible target for future treatments or interventions.

45. Cross-Sectional Exploratory Study of D-Serine Levels in Huntington’s Disease

Andrew McGarry1, Basant Pradhan1, Irving Wainer2
1Cooper University Healthcare at Rowan University, Department of Neurology, Camden, NJ, USA
2National Institute on Aging, Bethesda, MD, USA

Lay Summary: With no effective treatment for cognitive difficulties in HD, developing new approaches is an important focus in HD research. D-serine biology in an unexplored area in HD, with potential for application towards new treatment strategies in future clinical trials.

46. Huntington’s Disease Regulatory Science Consortium (HD-RSC): Enabling Pathways to Effective Treatments Through Regulatory Science and Innovation

Cheryl Fitzer-Attas1, Diane Stephenson2 Klaus Romero2, Volker D. Kern2, Cristina Sampaio1
1 CHDI Foundation, Princeton, NJ
2Critical Path Institute, Tucson, AZ

Lay Summary: Therapeutic development in HD has accelerated at an unprecedented pace with the advancement of many new candidate therapeutics that hold hope for patients and families in urgent need.  Yet risks for drug developers are high. Access to sufficient number of patients for trials is limited, and the field lacks a defined set of drug development tools that can aid them in advancing targets to the clinic. This presentation will highlight the groundwork and plans for a new consortium, the Huntington’s Disease Regulatory Science Consortium (HD-RSC).  Co-founded by CHDI Foundation and Critical Path Institute the spirit of partnership and collaboration fuels the success of HD-RSC. The objective of HD-RSC is to establish a collaborative infrastructure of all stakeholders, under the advisement by worldwide regulatory agencies, to accelerate new safe and effective treatments for HD. HD-RSC aims to tackle a broad range of issues relevant to HD therapeutic development using a data driven strategy.  Data from completed HD drug trials (even those that failed) and observational cohorts can offer key insights to guide and improve ongoing and future HD drug development efforts, and accelerate the delivery of new therapies for those in need. The HD community is encouraged to learn more.

47. The FDA is Listening: Integrating the Voice of the Patient in Drug Development for Parkinson’s and Huntington’s Diseases

Diane Stephenson1, Klaus Romero1, Gerald Podskalny2, Eric Bastings2, Billy Dunn2, Susanne Goldstein2, Theresa Mullin2,
1 Critical Path Institute, Tucson, AZ
2 U.S. Food and Drug Administration (FDA)

 Lay Summary: There is growing interest in the importance of incorporating the patient perspective into the process of drug approval and evaluation.  This presentation highlights the FDA’s patient focused drug development meeting focused on Movement Disorders. The FDA conducted a public meeting in 2015 on Patient-Focused Drug Development for Huntington’s disease and Parkinson’s disease. Perspectives on the impact of Huntington’s disease and Parkinson’s disease on daily life was communicated by patients and care-partners.  Following the meeting, the FDA published a Voice of the Patient (VOP) report that summarizes the patient testimonies at the meeting. The full webcast and VOP report is available on the FDA website for viewing. The report serve an important function in communicating to both the FDA and regulated industry what improvements patients view as the most burdensome aspects of the disease on their daily lives as well as the unmet needs in terms of new treatments. FDA recognizes that patients have a unique ability to contribute to our understanding of the broader context of these diseases. The insight provided during these meetings will aid in FDA’s understanding of what patients truly value in a treatment and inform the agency’s evaluation of the benefits and risk of future treatments for PD and HD patients.

48. Factors Influencing Completion of Predictive Testing for Huntington’s Disease (HD)

Margi Patel1, Mahvish Ayman2, Victor Sung1
1University of Alabama (UAB), Birmingham, Alabama, USA
2Shadan Institute of Medical Sciences, Hyderabad, Telangana, India

Lay Summary: The possibility of changing national guidelines dictated by the World Federation of Neurology and International Huntington Association for predictive testing of HD is discussed.

49. Dysregulated Amino Acid Homeostasis and Signaling in Huntington’s Disease: Therapeutic Opportunities

Bindu D. Paul, Juan I. Sbodio, Solomon H. Snyder
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Lay Summary: A link between antioxidant defense mechanisms and amino acid imbalance has been established, which identifies additional points of therapeutic intervention.

50. Feasibility and Acceptability of Implementing a Clinic-Based Physical Activity Coaching Intervention in People with Premanifest and Early-Stage HD

Lori Quinn1, Karen Marder2, Monica Busse3
1Teachers College, Columbia University, NY, NY, USA
2Columbia University, NY, NY, USA
3Cardiff University, Cardiff, UK

Lay Summary: Exercise and physical activity have been shown to improve functional abilities, as well as motor and cognitive impairments, in people with HD; however, programs to encourage people with HD to exercise are not routinely implemented in clinic settings. We have developed a physical activity coaching program specifically designed for people with premanifest and early stage HD. This study will evaluate this program in 14 individuals with premanifest and early stage HD, and results will be used to inform a future larger scale study and ultimately to provide a structured approach that can be implemented by physical therapists and other healthcare professionals in HD clinic settings.

51. Influence of Cognitive and Motor Dual Tasks on Gait in Prodromal and Manifest Huntington’s Disease

Ashwini Rao, Karen Marder
Huntington’s Disease Center of Excellence, Columbia University, New York, NY, USA

Lay Summary: Huntington’s disease leads to impairments in motor and cognitive function. Functional mobility often requires concurrent performance of manual and cognitive tasks while walking. We examined whether performing cognitive and manual tasks during walking has an effect on quantitative measures of gait. We find that performing a cognitive task during walking results in highly variable stepping, which may increase future risk for falls. The results highlight the importance of assessing cognitive dual task during walking in the clinic.

52. Impaired Homeostatic Plasticity in YAC128 HD Mouse Cortical Neurons Rescued by Pridopidine

Amy Smith-Dijak1, James Mackay1, Michal Geva2, Michael Hayden2, Lynn A. Raymond1
1Department of Psychiatry and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
2Research and Development, Teva Pharmaceutical Industries, Netanya, Israel     

Lay Summary: In recent clinical trials, results suggest that Pridopidine may slow decline in the UHDRS total functional capacity, a measure of progression of Huntington’s disease. As well, the PREDICT-HD and TRACK-HD studies indicated impairments in mental flexibility and new learning in the earliest stages of Huntington’s disease. Our study used brain cells (neurons) from an HD mouse model to show that Pridopidine restores a form of neuronal plasticity that is critical for allowing new learning and mental flexibility.

53. A Qualitative Analysis of the Impact of Chorea on Health-Related Quality of Life in HD: Perspectives from Patients, Family Members, and Professional Providers

Carey Sherman1, Ravi Iyer2, Victor Abler2, Noelle E. Carlozzi3
1Institute for Social Research, University of Michigan, Ann Arbor, MI, USA
2Teva Pharmaceutical Industries, Frazer, PA, USA
3Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA

Lay Summary: Chorea can significantly impact day-to-day activities and health-related quality of life of individuals with HD. Understanding the nuances of these concerns may help inform management and intervention strategies and ultimately improve the health-related quality of life in these individuals.

54. Experience of Individuals With Huntington’s Disease and Chorea

Eileen Mack Thorley1, Ravi Iyer2, Noelle Carlozzi3, Paul Wicks1, Chris Curran1, Sanjay Gandhi2, Victor Abler2, Karen Anderson4
1PatientsLikeMe, Cambridge, MA, USA
2Teva Pharmaceutical Industries, Frazer, PA, USA
3Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA
4Georgetown University, Washington, DC, USA

Lay Summary: In individuals with HD, inadequate control of chorea and the associated anxiety and stigma negatively impact health-related quality of life. Based on responses from individuals with HD and HD caregivers, loss of independence, mobility issues, and unpredictability of chorea were identified as the most common reasons why chorea management is important.

55. Physician Perceptions of Unmet Medical Needs in Huntington’s Disease in the United States

Victor Sung1, Ravi Iyer2, Sanjay Gandhi2, Bijal Shah-Manek3, PhD; Marco DiBonaventura3, Victor Abler2, Daniel Claassen4
1University of Alabama School of Medicine, Birmingham, AL, USA
2Teva Pharmaceutical Industries, Frazer, PA, USA
3Ipsos Healthcare, San Francisco, CA, USA
4Vanderbilt University Medical Center, Nashville, TN, USA

Lay Summary: The side effects associated with tetrabenazine limit its use in treating HD-related chorea. The tolerability concerns with tetrabenazine highlight the need for alternate, more-tolerable, and efficacious therapeutic alternatives to tetrabenazine for the treatment of HD-related chorea.

56. Treatment Patterns and Unmet Medical Needs in Huntington’s Disease in the United States

Daniel O. Claassen1, Ravi Iyer2, Bijal Shah-Manek3, Marco DiBonaventura3, Victor Abler2, Victor Sung4
1Vanderbilt University Medical Center, Nashville, TN, USA
2Teva Pharmaceutical Industries, Frazer, PA, USA
3Ipsos Healthcare, San Francisco, CA, USA
4University of Alabama School of Medicine, Birmingham, AL, USA 

Lay Summary: Many patients with HD are unable to achieve adequate control of chorea with tetrabenazine due to an inability to tolerate treatment at efficacious doses. This suggests that a better-tolerated and efficacious treatment for this population is needed.

Initial Deutetrabenazine Compliance, Satisfaction, and Patient Perception of Change in Huntington Disease Symptoms

Victor W. Sung, MD1; Ravi Iyer, PhD, MBA2; Sanjay K. Gandhi, PhD2; Victor Abler, DO2; Kristen Bibeau, PhD, MSPH2; Daniel O. Claassen, MD3; Samuel Frank, MD4
1University of Alabama at Birmingham, Birmingham, Alabama, USA
2Teva Pharmaceutical Industries, Frazer, Pennsylvania, USA
3Vanderbilt University Medical Center, Nashville, Tennessee, USA
4Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, USA

No Lay Summary

57. Update on the LEGATO-HD Study: A Phase 2 Study Assessing the Efficacy and Safety of Laquinimod as a Treatment for Huntington’s Disease

Ralf Reilmann1, Mark Forrest Gordon2, Karen Anderson3, Andrew Feigin4, Sarah Tabrizi5, Blair Leavitt6, Julie Stout7, Paola Piccini8, Michael Gillespie2, Gail Rynkowski2, Sarah Swanson2, Juha Savola2, Spyros Papapetropoulos2, Beth Borowsky2, Michael Hayden2
1George-Huntington-Institute Muenster & Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Germnay
2Research and Development, Teva Branded Pharmaceuticals
3MedStar Georgetown University Hospital & Georgetown University Medical Center, Washington, DC, USA
4The Feinstein Institute for Medical Research, North Shore – LIJ Health System, Manhasset, NY, USA
5UCL Institute of Neurology, London, UK
6Centre for Huntington’s Disease, University of British Columbia, Canada
7Monash University, Australia
8Imperial College London, London, UK

Lay Summary: Update on the LEGATO-HD Study, a phase 2 study designed to evaluate the efficacy and safety of laquinimod, a CNS immunomodulator as a treatment for HD.

58. Predictors for Psychosis in Huntington’s Disease: Preliminary Analysis of the Enroll-HD Database

Natalia P Rocha1, Erin Furr Stimming2, Antonio L Teixeira1
1Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
2Movement Disorders & Neurodegenerative Diseases Program, Department of Neurology, The University of Texas Health Science Center at Houston, Houston, TX, USA

Lay Summary: Behavioral problems are present across all stages of HD. While not so frequent in HD, psychosis (dellusions and/or hallucinations) can be very distressful for both individuals with HD and their caregivers. Psychotic symptoms have been underinvestigated in HD, and this study was designed to evaluate their clinical predictors.

59. Cerebrospinal Fluid Flow Dynamics in Huntington’s Disease Using Phase Contrast MRI: A Pilot Cross-Sectional Study

Filipe B. Rodrigues1, Lauren M. Byrne1, Enrico de Vita2, Eileanoir Johnson1, Rachael Scahill1, Edward J. Wild1
1Huntington’s Disease Centre, University College London, UK
2National Hospital for Neurology & Neurosurgery, UCLH NHS Trust, UK

Lay Summary: Findings from laboratory research suggest that the flow of cerebrospinal fluid may be altered in Huntington’s disease. This pilot study used a novel magnetic resonance imaging technique to study the flow of CSF in 10 people with Huntington’s disease and 10 healthy controls, and found no differences between the groups. These results need to be replicated elsewhere but offer reassurance that CSF flow is not altered in HD, which is useful information in planning future trials of drugs that need to be injected into the CSF.

60. Perinatal Insults and Neurodevelopmental Disorders May Impact Age of Diagnosis of Huntington’s Disease

Melinda Barkhuizen1,2,3, Filipe Rodrigues4,5,6, David G. Anderson7, Edward J. Wild4, Boris W. Kramer1,2,8, A.W. Danilo Gavilanes1,2,9
1Department of Pediatrics, Maastricht University Medical Center (MUMC), Maastricht, The Netherlands
2Department of Translational Neuroscience, School of Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands
3DST/NWU Preclinical Drug Development Platform, North-West University, Potchefstroom, South Africa
4Huntington’s Disease Centre, Institute of Neurology, University College London, London, UK
5Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal
6Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
7Department of Neurology, University of the Witwatersrand Donald Gordon Medical Centre, Johannesburg, South Africa
8School of Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
9Institute of Biomedicine, Facultad de Ciencias Médicas, Universidad Católica de Santiago de Guayaquil, Ecuador

Lay Summary: Age of disease onset in HD might be impacted by events that occur in early life. Using data from two large observation studies, REGISTRY and Enroll-HD, we found that HD mutation carriers who experienced medical difficulties around the time of their birth, or disorders of brain development, tended to develop HD symptoms several years earlier. These findings emphasize the potential impact of early-life events on the course of HD and the need to study and minimize them.

61. Behavioral Testing of Minipigs Transgenic for the Huntington Gene: A Three-Year Follow-Up Study

Verena Schuldenzucker1,2, Robin Schubert1, Lisa Muratori3, Frauke Freisfeld1,4, Lorena Rieke1,5,  Tamara Matheis1,5, Sarah Schramke1, Nicole Kemper5, Ute Radespiel2, Ralf Reilmann1,4,6
1George-Huntington-Institute, Technology-Park, Johann-Krane-Weg 27, Muenster, Germany
2Institute of Zoology, University of Veterinary Medicine Hannover, Hannover, Germany
3Department of Physical Therapy, School of Health Technology and Management, Stony Brook University, Stony Brook, NY, USA
4Department of Clinical Radiology, University of Muenster, Muenster, Germany
5Institute of Animal Hygiene, Animal Welfare and Farm Animal Behavior, University of Veterinary Medicine Hannover, Hannover, Germany
6Department of Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany

Lay Summary: Prior to testing novel drugs in human clinical trials, they are tested in preclinical studies to explore safety, tolerability, and efficacy. Large-animal models may provide a more reliable translation into humans because they exhibit a high genetic homology and similar body and brain structure. The assessment battery presented offers a feasible and sensitive set of measures for a continuous phenotyping of the tgHD minipig model or other pig models.

62. Patient Preferences for Risk-Benefit Assessment of Huntington’s Disease

Natasha Scott1, Karen Anderson2, Erin Wilhelm3, Ira Shoulson4
1Georgetown University, Washington, DC, USA
2Medstar Georgetown University Hospital and Georgetown University, Department of Psychiatry and Department of Neurology, Washington, DC, USA
3Georgetown University, Department of Pharmacology & Physiology, Washington, DC, USA
4Georgetown University Medical Center, Department of Neurology, Washington, DC, USA

Lay Summary: Two focus groups were held to learn more about how HD patients weigh risks and benefits when they compare potential treatment options. Participants reported that they prioritized impaired balance, cognition, and emotion over other symptoms. This information could inform the design of medical care and research.

63. Comparative Retrospective Analysis of Tetrabenazine and Olanzapine in Management of Huntington’s Disease Based on Data from the Worldwide Observational Study Enroll-HD

Yury Seliverstov 1 Artyom Borzov 2,3, Ravil Niyazov 5, Mikhail Belyaev 2,4
1Department of Neurogenetics, Research Center of Neurology, Moscow, Russian Federation
2Institute for Information Transmission Problems (Kharkevich Institute), Moscow, Russian Federation
3Moscow Institute of Physics and Technology, Moscow, Russian Federation
4Skolkovo Institute of Science and Technology, Moscow, Russian Federation
5Center for Scientific Advice Ltd, Moscow, Russian Federation  

Lay Summary: Olanzapine is one of the widely prescribed neuroleptics in HD. To our knowledge, no comparisons of any kind of tetrabenazine and olanzapine have been published so far. We report data.

64. Evaluating Wearable Sensors for Objective Measurement of Motor Features of Huntington Disease

Jamie Adams1, Karthik Dinesh2, Mulin Xiong1, Christopher Snyder1, Christopher A. Tarolli1, Saloni Sharma1, Nirav Sheth3, A.J. Aranyosi3, William Zhu1, Steven Goldenthal1, Kevin Biglan1, Ray Dorsey1, Gaurav Sharma2
1Center for Health + Technology, University of Rochester, Rochester, NY, USA,
2University of Rochester, Rochester, NY, USA
3MC10 Inc., Lexington, MA, USA

Lay Summary: Objective measures of motor function in HD are lacking. With increasingly accurate tools to assess symptoms, we can more quickly identify potential treatments. We are testing a wearable sensor system that has been able to differentiate the gait and lifestyle features of individuals with and without HD. This research has the potential to dramatically speed up clinical trials and the development of new therapeutics for HD.

65. Cerebrospinal Fluid Mutant Huntingtin Concentration: What Does it Mean?

Nicholas Caron1, Christopher Yanick2, Stephen E.P. Smith3, Yuanyun Xie1, Ji Joon Song4, Ihnsik Seong5, Blair R. Leavitt1, Michael R. Hayden1, Amber L. Southwell2
1Center for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
2Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA
3Seattle Children’s Research Institute, University of Washington, Seattle, WA, USA
4Department of Biological Sciences, KAIST, Daejeon, Korea
5Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

Lay Summary: Mutant huntingtin protein level in spinal fluid is currently being used in a clinical trial to evaluate the effectiveness of a therapy to reduce huntingtin protein in the brains of people with HD. We are studying where mutant huntingtin in the spinal fluid originates and how it gets there so that we can understand the meaning of changes in the protein level.

66. Feasibility of Smartphone Application Use for the Objective Evaluation of the Effects of Huntington’s Disease’s on Motor Function

Kelsey L. Spear, Jamie L. Adams, Molly J. Elson, Tyler S. Geery, Michael J. Curtis, David J. Mitten, E. Ray Dorsey
University of Rochester Medical Center, Rochester, NY, USA

Lay Summary: George, the first smartphone application for HD, was developed to quantify motor symptoms of HD, distinguish between individuals with and without HD, and assess the response to drug treatment. A pilot study of the George smartphone application will result in further refinement of the application based on participant feedback and data collected, and ideally lay the foundation for its use in evaluating the efficacy of current and future therapies for HD.

67. Tracking Huntington’s Disease in Italian Premanifest and Manifest Subjects by Connecting REGISTRY and Enroll-HD Observational Studies

Ferdinando Squitieri1, Sabrina Maffi1, Simone Migliore1,2, Massimo Marano1,2, Irene Mazzante2, Iolanda Santimone1, Francesca Lovo2, Barbara D’Alessio2
1Huntington and Rare Diseases Unit, IRCCS Casa Sollievo della Sofferenza Hospital (San Giovanni Rotondo), CSS-Mendel, Rome, Italy
2LIRH Foundation, Rome, Italy

Lay Summary: We need to seek new possible factors that may impact development and progression of HD from premanifest to advanced life stages. Observational prospective analyses are crucial to learn how the disease changes overtime.

68. Efficient Genome Editing in the Mouse Brain by Local Delivery of Engineered Cas9

Brett T. Staahl1, Madhurima Benekareddy2, Claire Coulon-Bainier2, Ashwin A. Banfal1, Stephen N. Floor1, Jennifer K. Sabo1, Cole Urnes1, Gabriela Acevedo Munares1, Anirvan Ghosh2,3, Jennifer A. Doudna1,4,7
1Department of Molecular and Cell Biology, University of California, Berkeley, California, USA 2Roche Pharma Research and Early Development, Basel, Switzerland
3E-Scape Bio, San Francisco, California, USA
4Howard Hughes Medical Institute, University of California, Berkeley, California, USA 5Innovative Genomics Institute, University of California, Berkeley, California, USA
6MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA
7Department of Chemistry, University of California, Berkeley, California, USA

Lay Summary: Researchers sought to mitigate complications by using Cas9 in a transient way. They engineered Cas9 so it inserts into cells as a functioning enzyme. When injected into the brains of mice it deleted a segment of DNA in neurons. Unlike genetically encoded, this Cas9 rapidly degraded, preventing long-term consequences.

69. Microglia Mediate Early Loss of Specific Synaptic Connections in Huntington’s Disease

D.K. Wilton1, M. Heller1, A. Daggett2, A.Y. Kim1, A. Frouin1, M. Eszes3, R. Faull3, W.X. Yang2, B. Stevens1
1Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
2Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behaviors, David Geffen School of Medicine at University of California, Los Angeles, CA, USA
3The University of Auckland, Grafton, Auckland, New Zealand

Lay Summary: Several studies have shown that the immune system is perturbed in Huntington’s disease (HD); however, the underlying mechanisms involved and the degree to which they play a role in disease pathogensis remain unclear. Our study shows that in multiple mouse models of HD, elements of the innate immune system—including complement, a group of immune proteins associated with clearance of dying cells, and microglia, the brain’s resident immune cells—play a role in the selective loss of synaptic connections between the cortex and striatum.

70. “I Have a Feeling I Can’t Speak to Anybody”: A Thematic Analysis of Communication Perspectives in People with Huntington’s Disease

Nicolò Zarotti, Jane Simpson, Ian Fletcher
Division of Health Research, Faculty of Health and Medicine, Lancaster University, UK

Lay Summary: Research in neuropsychology of HD has allowed us to gain invaluable understanding of how the disease affects language and speech from a clinical perspective. However, very little is currently known about the subjective experiences of patients when communicating with their significant others. This study tried to fill this gap by carrying out a qualitative investigation of the perspectives of people with HD on their own communicative abilities. The findings have the potential to help us improve communication among clinicians, caregivers, and patients, as well as to tailor interventions around the communicative and emotional needs of affected people.

71. Selection of an AAV Gene Therapy Targeting Huntingtin for the Treatment of Huntington’s Disease

Pengcheng Zhou1, Fen Chen1, Xin Wang1, Emily Christensen1, Jeff Thompson1, Mathieu Nonnenmacher1, Maria Scheel1, Xiao Ren1, Wei Wang1, Xiaochuan Zhou1, Lisa Stanek2, Bryan Mastis2, Peter Pechan1, Eric Horowitz1, David Dismuke1, Adrian Kells1, Todd Carter1, Jay Hou1, Dinah Sah1
1Voyager Therapeutics, Inc., Cambridge, MA, USA
2Sanofi/Genzyme, Framingham, MA, USA

Lay Summary: HD is caused by a genetic mutation resulting in a toxic huntingtin (HTT) protein. Here, we describe a series of studies to develop an AAV gene therapy that selectively reduces HTT for the treatment of HD.

72. A Pilot Study Evaluating Plasma Endocannabinoid Levels as Biomarkers in Huntington’s Disease

Grace Zimmerman1, Peter Morrison1, Kevin Welle1, Jennifer Hryhorenko1, Stephen D’Ambrosio1, Iris Young1, Michael McDermott1, Kevin Biglan1, Kelly L. Andrzejewski1,2
1Department of Neurology, University at Buffalo, Buffalo, NY, USA
2Department of Neurology, University of Rochester, Rochester, NY, USA

No Lay Summary

73. Genotype-Phenotype Correlation of Huntingtin CAG Repeat Expansion and Associated Symptoms in a Large Indian Family Carrying Huntington’s Disease Mutation

Roshni Kishor Bhatt1, Sudhir V. Shah2, Hitarthi Vyas1, Ravi Vijayvargiya1
1Department of Biochemistry, The Maharaja Sayajirao University of Baroda, Vadodara India
2Department of Neurology, Seth K M School of Postgraduate Medicine and Research, Ahmedabad, India     

Lay Summary: This study tries to make a point that HD is prevalent in India but largely undiagnosed due to lack of education and awareness. There is a need to carry out large-scale population studies to determine the exact prevalence and to introduce measures for improving awareness and proper genetic counselling to prevent its spread.

74. Molecular and Cellular Assessment of HTT Lowering in Differentiated Patient-Derived HD iPS Cells

Lisa L. Salazar1, Ryan G. Lim2, Andrea M. Reyes-Ortiz2, Sarah J. Hernandez3, Charlene Geater1, Austin Hill4, Julia A. Kaye5, Jennifer T. Stocksdale6, Keona Wang3, Lexi K. Kopan3, Steven Finbeiner 5,7, Blair Leavitt4, Leslie M. Thompson1,2,3,6,8
1 Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, California, USA.
2Department of Biological Chemistry, University of California, Irvine, Irvine, California, USA.
3 Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California, USA.
4Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada V5Z 4H4.
5Gladstone Institutes and the Taube/Koret Center of Neurodegenerative Disease Research, Roddenberry Stem Cell Research Program, San Francisco, California, USA.
6UCI MIND, University of California, Irvine, Irvine, California, USA.
7 Departments of Neurology and Physiology, University of California, San Francisco, San Francisco, California, USA.
8Sue and Bill Gross Stem Cell Center, University of California, Irvine, Irvine, California, USA

Lay Summary: Initial reports from the current clinical trial of IONIS-HTTRx, which lowers total Huntingtin (HTT) protein, are encouraging, and efforts are also underway for clinical application of selectively lowering mutant HTT. A key question remains as to whether reducing total HTT will be sufficient to alleviate disease, or whether preferential reduction of mutant HTT will be more effective. Our work evaluates the potential of total versus mutant HTT lowering to correct cellular and gene expression changes in HD iPSC-derived neurons, which will provide information regarding these HTT-lowering treatments.