Novak MW, Tabrizi SJ. Huntington’s disease. BMJ. 2010;340:c3109.
Abildtrup M, Shattock M. Cardiac dysautonomia in Huntington's disease. J Huntingtons Dis. 2013;2:251-261. Abstract
Roos RAC. Huntington's disease: a clinical review. Orphanet J Rare Dis. 2010;5:40.
Røthing M, Malterud K, Frich JC. Caregiver roles in families affected by Huntington's disease: a qualitative interview study. Scand J Caring Sci. 2014;28:700-705. Abstract
Frank S. Treatment of Huntington’s Disease. Neurotherapeutics. 2014;11:153-160. Abstract
Gonzalez V, Cif L, Biolsi B, et al. Deep brain stimulation for Huntington's disease: long-term results of a prospective open-label study. J Neurosurg. 2014;121:114-122. Abstract
Armstrong MJ, Miyasaki JM; American Academy of Neurology. Evidence-based guideline: pharmacologic treatment of chorea in Huntington disease: report of the guideline development subcommittee of the American Academy of Neurology. Neurology. 2012;79:597-603. Abstract
Frank SA; First-HD Investigators of the Huntington Study Group. First time use of SD-809 in Huntington Disease (First-HD). Paper presented at: 67th Annual Meeting of the American Academy of Neurology; April 18-25, 2015; Washington, DC.
ClinicalTrials.gov. Alternatives for Reducing Chorea in HD (ARC-HD). NCT01897896. https://clinicaltrials.gov/ct2/show/NCT01897896. Accessed July 4, 2016.
de Yebenes JG, Landwehrmeyer B, Squitieri F, et al. Pridopidine for the treatment of motor function in patients with Huntington's disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2011;10:1049-1057. Abstract
ClinicalTrials.gov. A Phase 2, to Evaluating the Safety and Efficacy of Pridopidine Versus Placebo for Symptomatic Treatment in Patients With Huntington's Disease. NCT02006472. https://clinicaltrials.gov/ct2/show/NCT02006472. Accessed July 4, 2016.
Mayo Clinic. Huntington’s disease: Treatments and drugs. http://www.mayoclinic.org/diseases-conditions/huntingtons-disease/basics/treatment/con-20030685. Published July 24, 2014. Accessed July 4, 2016.
ClinicalTrials.gov. A Clinical Study in Subjects With Huntington's Disease to Assess the Efficacy and Safety of Three Oral Doses of Laquinimod (LEGATO-HD). NCT02215616. https://clinicaltrials.gov/ct2/show/NCT02215616. Accessed July 10, 2016.
ClinicalTrials.gov. Multicentric Trial of the Treatment of Huntington’s Disease by Cysteamine (RP103). NCT02101957. https://clinicaltrials.gov/ct2/show/NCT02101957. Accessed July 10, 2016.
Sah DW, Aronin N. Oligonucleotide therapeutic approaches for Huntington’s Disease. J Clin Investig. 2011;121:500-507. Abstract
Zuccato C, Valenza M, Cattaneo E. Molecular mechanisms and potential therapeutic targets in Huntington’s Disease. Physiol Rev. 2010;90:905-981. Abstract
Walker FO. Huntington’s disease. Lancet. 2007;369:218-228. Abstract
Sampaio C, Borowsky B, Reilmann R. Clinical trials in Huntington's disease: Interventions in early clinical development and newer methodological approaches. Mov Disord. 2014;29:1419-1428. Abstract
Ross CA, Aylward EH, Wild EJ, et al. Huntington’s disease: natural history, biomarkers and prospects for therapeutics. Nat Rev Neurol. 2014;10:204-216. Abstract
Tabrizi SJ, Langbehn DR, Leavitt BR, et al. Biological and clinical manifestations of Huntington’s disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data. Lancet Neurol. 2009;8:791-801. Abstract
Tabrizi SJ, Scahill RI, Owen G, et al. Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington’s disease in the TRACK-HD study: analysis of 36-month observational data. Lancet Neurol. 2013;12:637-649. Abstract
Paulsen JS, Long JD, Johnson HJ, et al. Clinical and biomarker changes in premanifest Huntington disease show trial feasibility: a decade of the PREDICT-HD study. Front Aging Neurosci. 2014;6:78.
ClinicalTrials.gov. Enroll-HD: A Prospective Registry Study in a Global Huntington's Disease Cohort. NCT01574053. https://clinicaltrials.gov/ct2/show/NCT01574053. Accessed July 4, 2016.

CPD

Are We Making Progress in the Management of Huntington Disease?

Authors: Ralf Reilmann, MD; Samuel A. Frank, MD; G. Bernhard Landwehrmeyer, MD, PhD, FRCP; Claudia M. Testa, MD, PhD
CPD Released: 8/16/2016
THIS ACTIVITY HAS EXPIRED FOR CREDIT
Valid for credit through: 8/16/2017

Target Audience and Goal Statement

This educational activity is intended for an international audience of healthcare professionals, specifically neurologists, primary care physicians (PCPs), orthopedists and orthopedic surgeons, internists, psychiatrists, and other healthcare professionals who provide care for people with Huntington disease (HD).

The goal of this activity is to increase participants’ knowledge of the burden of HD; current treatment options for motor and other symptoms, in particular chorea; and new therapies in development, including the role of biomarkers, neuroimaging, and quantitative motor assessments.

Upon completion of this activity, participants will:

Have increased knowledge regarding the:

Burden of HD on patients, caregivers, and society
Current and emerging therapies for HD, including the role of biomarkers and quantitative motor assessments

Have greater competence related to:

The management of chorea and other symptoms of HD, and the role of a team-based approach

Disclosures

WebMD Global requires each individual who is in a position to control the content of one of its educational activities to disclose any relevant financial relationships occurring within the past 12 months that could create a conflict of interest.

Moderator

Ralf Reilmann, MD

Founding Director, George-Huntington-Institut Department of Radiology, University of Münster, Münster, Germany; Department of Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

Disclosures

Disclosure: Ralf Reilmann, MD has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: AOP Orphan Pharmaceuticals AG; Desitin Arzneimittel GmbH; H. Lundbeck A/S; Ionis Pharmaceuticals, Inc. (FKA Isis); Ipsen; Isis Pharmaceuticals, Inc.; Link Medicine; MEDA Pharmaceuticals, Inc.; Medivation, Inc.; Novartis Pharmaceuticals Corporation; Omeros; Pfizer Inc.; Prana Biotechnology; Raptor Pharmaceutical, Inc.; Siena Biotech; Temmler Werke GmbH; Teva Neuroscience, Inc.; The Cure Huntington’s Disease Initiative Foundation; uniQure; Vaccinex; Wyeth Pharmaceuticals Inc.
Served as a speaker or a member of a speakers bureau for: AOP Orphan Pharmaceuticals AG; Desitin Arzneimittel GmbH; Ionis Pharmaceuticals, Inc. (FKA Isis); Ipsen; Isis Pharmaceuticals, Inc.; Link Medicine; H. Lundbeck A/S; MEDA Pharmaceuticals, Inc.; Medivation, Inc.; Novartis Pharmaceuticals Corporation; Omeros; Pfizer Inc.; Prana Biotechnology; Raptor Pharmaceutical, Inc.; Siena Biotech; Temmler Werke GmbH; Teva Neuroscience, Inc.; The Cure Huntington’s Disease Initiative Foundation; uniQure; Vaccinex; Wyeth Pharmaceuticals Inc.
Received grants for clinical research from: Bundesministerium für Bildung und Forschung; CHDI Foundation, Inc.; Deutsche Forschungsgemeinschaft; Deutsches Zentrum für Neurodegeneration und Entzündung; European Huntington’s Disease Network; European Union (EU-FP7 program); High-Q-Foundation
Other: Director and Owner of: George-Huntington-Institut; QuantiMedis

Faculty

Samuel A. Frank, MD

Associate Professor, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States

Disclosures

Disclosure: Samuel A. Frank, MD, has disclosed the following relevant financial relationships:
Received grants for clinical research from: Teva Pharmaceuticals Industries Ltd.

Bernhard Landwehrmeyer, MD, PhD, FRCP

Professor of Neurology, Clinical Neurobiology, Ulm University Hospital, Ulm, Germany

Disclosures

Disclosure: Bernhard Landwehrmeyer, MD, PhD, FRCP, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Desitin Arzneimittel GmbH; Ionis Pharmaceuticals, Inc. (FKA Isis); Pfizer Inc.; Raptor Pharmaceutical, Inc.; Roche; Siena Biotech; Teva Europe
Served as a speaker or a member of a speakers bureau for: Desitin Arzneimittel GmbH; MDJ
Received grants for clinical research from: Bundesministerium für Bildung und Frauen; CHDI Foundation, Inc.; EC

Claudia M. Testa, MD, PhD

Associate Professor, Director, VCU Huntington Disease Program, Huntington’s Disease Society of America Centre of Excellence, Virginia Commonwealth University, Richmond, Virginia, United States

Disclosures

Disclosure: Claudia M. Testa, MD, PhD, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Lundbeck, Inc.
Received grants for clinical research from: CHDI Foundation, Inc. (nonprofit); NIH/NORD; Teva Pharmaceutical Industries Ltd.

Steering Committee

Giancarlo Comi, MD

Professor of Neurology, Chairman, Specialization School in Neurology, University Vita-Salute San Raffaele; Director, Department of Neurology, Scientific Institute San Raffaele, Milan, Italy

Disclosures

Disclosure: Giancarlo Comi, MD (Chair), has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Almirall, S.A.; Bayer HealthCare; Biogen Idec Inc.; Chugai Pharma USA, LLC; Excemed; Genzyme Corporation; Merck Serono; Novartis Pharmaceuticals Corporation; Receptos; Roche; Sanofi; Serono Symposia Int. Foundation; Teva Europe
Served as a speaker or a member of a speakers bureau for: Almirall, S.A.; Bayer HealthCare; Biogen Idec Inc.; Chugai Pharma USA, LLC; Excemed; Genzyme Corporation; Merck & Co., Inc.; Merck Serono; Novartis Pharmaceuticals Corporation; Receptos; Sanofi; Serono Symposia Int. Foundation; Teva Europe

Kevin M. Biglan, MD

Professor of Neurology, Associate Chair of Clinical Research Movement Disorders Division, University of Rochester Medical Center, Rochester, New York, United States

Disclosures

Disclosure: Kevin M. Biglan, MD, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: KJT Consulting Services; UCB Pharma, Inc.
Received grants for clinical research from: Lundbeck, Inc.

Patricia K. Coyle, MD

Professor, Department of Neurology; Vice Chair, Clinical Affairs; Director, Multiple Sclerosis Comprehensive Care Center, Stony Brook University Medical Center, Stony Brook, New York, United States

Disclosures

Disclosure: Patricia K. Coyle, MD, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: AbbVie Inc.; Accordant; Acorda Therapeutics; Bayer HealthCare; Biogen Idec Inc.; Genentech, Inc.; Genzyme Corporation; Mallinckrodt Pharmaceuticals; Merck Serono; Novartis Pharmaceuticals Corporation; Roche; Sanofi; Teva Neuroscience, Inc.
Received grants for clinical research from: Actelion Pharmaceuticals, Ltd; Genentech, Inc.; Novartis Pharmaceuticals Corporation; Opexa Therapeutics, Inc.; Roche

G. Bernhard Landwehrmeyer, MD, PhD, FRCP

Disclosures

As listed above.

Tiago A. Mestre, MD, MSc

Assistant Professor, Division of Neurology, Department of Medicine, University of Ottawa; Researcher, Ottawa Hospital Research Institute, Brain and Mind Research Institute, Medical Director, Enroll-HD; Chair, Committee on Review of HD Rating Scales, International Parkinson’s Disease and Movement Disorders Society, Ottawa, Ontario, Canada

Disclosures

Disclosure: Tiago A. Mestre, MD, MSc, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: AbbVie Inc.
Served as a speaker or a member of a speakers bureau for: Teva Pharmaceutical Industries Ltd

Editor

Gillian Griffith, BA (Mod), MA

Scientific Director, WebMD Global, LLC

Disclosures

Disclosure: Gillian Griffith, BA (Mod), MA, has disclosed no relevant financial relationships.

Content Reviewer

Amy Bernard, MS, BSN, RN-BC

Lead Nurse Planner, Medscape, LLC

Disclosures

Disclosure: Amy Bernard, MS, BSN, RN-BC, has disclosed no relevant financial relationships.

Accreditation Statements

For Physicians

The Faculty of Pharmaceutical Medicine of the Royal Colleges of Physicians of the United Kingdom (FPM) has reviewed and approved the content of this educational activity and allocated it 0.50 continuing professional development credits (CPD).

Contact WebMD Global

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information about your eligibility to claim credit, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent participating in the activity. To successfully earn credit, participants must complete the activity online during the credit eligibility period that is noted on the title page.

Follow these steps to claim a credit certificate for completing this activity:

Read the information provided on the title page regarding the target audience, learning objectives, and author disclosures, read and study the activity content and then complete the post-test questions. If you earn a passing score on the post-test and we have determined based on your registration profile that you may be eligible to claim CPD credit for completing this activity, we will issue you a CPD credit certificate.
Once your CPD credit certificate has been issued, you may view and print the certificate from your CME/CE Tracker. CPD credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of the Medscape Education homepage.

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*The credit that you receive is based on your user profile.

From Medscape Education Neurology & Neurosurgery

CPD

Are We Making Progress in the Management of Huntington Disease?

Authors: Ralf Reilmann, MD; Samuel A. Frank, MD; G. Bernhard Landwehrmeyer, MD, PhD, FRCP; Claudia M. Testa, MD, PhDFaculty and Disclosures

THIS ACTIVITY HAS EXPIRED FOR CREDIT

CPD Released: 8/16/2016

Valid for credit through: 8/16/2017

processing....

Are We Making Progress in the Management of Huntington Disease?
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Slide 1.

Faculty
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Slide 2.

Program Overview
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Slide 3.

Burden of HD on Patients^[1]
- In the clinical field, motor symptoms may not be the ones that most affect patients with Huntington disease (HD)
[ CLOSE WINDOW ]

Slide 4.

Burden of HD on Patients (cont)^[1-3]
- Behavioral or psychiatric symptoms need to be identified in our patients, because they can be really damaging to both family life and work life
- Claudia M Testa, MD, PhD: In my clinic, I often use a dietitian or a nutritionist to try to maintain the patient’s weight in a positive way
- There are a lot more motor symptoms than chorea, and they need to be addressed to help patients with daily life
- Before the onset of motor symptoms, there may be behavioral and cognitive issues that can be just as impairing as the physical problems, not just for the person with HD, but for the whole family system
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Slide 5.

Burden of HD on Caregivers and Society^[4]
- The direct burden comes from someone who is sick and using hospitals, clinics, and other services
- HD is a disease of the young, so the patient may no longer be able to work; it may also remove a family member from the working environment
- The majority of people with HD are affected when they are starting careers or managing young children
  - So you have an adult member of the household who is slowly letting go of their contributions to society
- A huge cost is incurred when patients have to hire caregivers
- The impact the disease has on children as they grow up also needs to be considered
- It is important to take loss of income into account
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Slide 6.

Treatments for HD^[1,5-6]
- The only agency-approved treatment for chorea, or really any symptom of HD, is tetrabenazine
  - It suppresses the choreiform movements quite well
  - It has to be dosed a certain way, and patients need to be monitored for side effects
- But it is only one piece of the puzzle in terms of how the symptoms of HD are addressed
- Equally important is the lack of voluntary movement, so people are slowed down; they find daily tasks burdensome and difficult to execute
- Physiotherapy programs help manage these symptoms to some extent
- Amantadine is used by some clinicians to manage chorea, depending on the emotional state of the patient^[7]
- For some people, experimental treatments, including deep brain stimulation, are options currently being explored, maybe as a last resort for minimizing damaging high-amplitude involuntary movements
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Slide 7.

Deutetrabenazine: FIRST-HD Trial^[8]
- The FIRST-HD trial had pretty broad entry criteria
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Slide 8.

Deutetrabenazine: Safety Profile^[8-9]
- The aim of using deuterium is to alter the enzyme breakdown and to be able to use a lower dose that would prevent peak dose side effects
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Slide 9.

Deutetrabenazine: Impact on Patient^[8]
- There is so much that can now be done to improve function and quality of life for patients with HD
- HD is a dynamic disease, and the patient’s medication needs to be reassessed regularly
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Slide 10.

Pridopidine: Control of Voluntary Motor Coordination in HD^[10]
- Pridopidine for the control of voluntary motor coordination has been studies in two trials
- The Enroll-HD study was conducted in Europe by the European Huntington's Disease Network
- Its result was pretty much exactly reproduced by the HART study, conducted by the Huntington Study Group
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Slide 11.

Pridopidine: PRIDE-HD Study^[11]
- The PRIDE-HD study is exploring whether an extended dose range of pridopidine is associated with additional benefits for the motor phenotype and whether that translates into real-life benefit for patients
- It is hoped that pridopidine will be complementary to current treatments for the management of motor impairment
- Prior to the study results being communicated, conclusions cannot be made regarding the benefits of pridopidine
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Slide 12.

Potential Impact of Improvements in One Symptom on Other Symptoms^[1,12]
- If an improvement can be made on irritability or mood lability, an improvement can be made on overall motor function or chorea
- Now, the patient is more able to use occupational therapy to maintain their independence or physical therapy to improve and maintain their gait and balance
- Dr Testa: I am always reaching out to different partners: primary care physicians (PCPs) to check that the medications are going to work together, or therapists who are often closer to home than I am for patients.
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Slide 13.

The Role of PCPs in Treating HD^[1,4,12]
- To take care of HD patients in the best possible way, a team of professionals is needed
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Slide 14.

The Role of PCPs in Treating HD (cont)^[1,4,12]
- Dr Testa: When patients are having trouble with swallowing, I often working with a pharmacist, an idea I got from a community family medicine provider
- HD is a progressive disorder, but not every aspect of the disease is linearly progressive, eg, chorea
- It is important that patient medication is regularly reviewed
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Slide 15.

Strategies for Developing New HD Therapies^[1,13-16]
- There are very good animal models that may help develop new disease-modifying treatments for HD
- There are quite a few strategies investigating different biological pathways
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Slide 16.

Strategies for Developing New HD Therapies (cont)^[1,17-19]
- Some people are being overlooked because they have no symptoms or very subtle symptoms of HD
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Slide 17.

Structural Changes in Brain Prior to Emergence of HD Symptoms^[20-22]
- As everyone with the huntingtin (htt) expansion mutation will eventually develop HD, the disease serves as a model for the early stages of neurodegenerative diseases
- The large natural history studies, PREDICT-HD and TRACK-HD, have shown that at least 10 years prior to the emergence of diagnostic motors symptoms and signs, there are major changes in the brain
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Slide 18.

Future Developments in HD Treatment^[1,19]
- We are all hoping for an intervention that goes to the root cause of HD
- But other things, like appropriate training, are steps toward improving the situation for people at the prodromal stage
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Slide 19.

Concluding Remarks^[23]
- In Enroll-HD, patients can be enrolled for annual visits and can see whether they qualify for clinical developments in the future
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Slide 20.

Concluding Remarks (cont)
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Slide 21.

Thank You
[ CLOSE WINDOW ]

Slide 22.

This content has been condensed for improved clarity.

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Disclaimer

The educational activity presented above may involve simulated case-based scenarios. The patients depicted in these scenarios are fictitious and no association with any actual patient is intended or should be inferred.

The material presented here does not necessarily reflect the views of WebMD Global, LLC or companies that support educational programming on medscape.org. These materials may discuss therapeutic products that have not been approved by the European Medicines Agency for use in Europe and off-label uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies described in this educational activity.

References

Faculty and Disclosures

Moderator

Ralf Reilmann, MD

Faculty

Samuel A. Frank, MD

Bernhard Landwehrmeyer, MD, PhD, FRCP

Claudia M. Testa, MD, PhD

Steering Committee

Giancarlo Comi, MD

Kevin M. Biglan, MD

Patricia K. Coyle, MD

G. Bernhard Landwehrmeyer, MD, PhD, FRCP

Tiago A. Mestre, MD, MSc

Editor

Gillian Griffith, BA (Mod), MA

Content Reviewer

Amy Bernard, MS, BSN, RN-BC

CPD

Are We Making Progress in the Management of Huntington Disease?

Target Audience and Goal Statement

Disclosures

Moderator

Ralf Reilmann, MD

Faculty

Samuel A. Frank, MD

Bernhard Landwehrmeyer, MD, PhD, FRCP

Claudia M. Testa, MD, PhD

Steering Committee

Giancarlo Comi, MD

Kevin M. Biglan, MD

Patricia K. Coyle, MD

G. Bernhard Landwehrmeyer, MD, PhD, FRCP

Tiago A. Mestre, MD, MSc

Editor

Gillian Griffith, BA (Mod), MA

Content Reviewer

Amy Bernard, MS, BSN, RN-BC

Accreditation Statements

For Physicians

Instructions for Participation and Credit

Are We Making Progress in the Management of Huntington Disease?

Are We Making Progress in the Management of Huntington Disease?

Slide 1.

Faculty

Slide 2.

Program Overview

Slide 3.

Burden of HD on Patients[1]

Slide 4.

Burden of HD on Patients (cont)[1-3]

Slide 5.

Burden of HD on Caregivers and Society[4]

Slide 6.

Treatments for HD[1,5-6]

Slide 7.

Deutetrabenazine: FIRST-HD Trial[8]

Slide 8.

Deutetrabenazine: Safety Profile[8-9]

Slide 9.

Deutetrabenazine: Impact on Patient[8]

Slide 10.

Pridopidine: Control of Voluntary Motor Coordination in HD[10]

Slide 11.

Pridopidine: PRIDE-HD Study[11]

Slide 12.

Potential Impact of Improvements in One Symptom on Other Symptoms[1,12]

Slide 13.

The Role of PCPs in Treating HD[1,4,12]

Slide 14.

The Role of PCPs in Treating HD (cont)[1,4,12]

Slide 15.

Strategies for Developing New HD Therapies[1,13-16]

Slide 16.

Strategies for Developing New HD Therapies (cont)[1,17-19]

Slide 17.

Structural Changes in Brain Prior to Emergence of HD Symptoms[20-22]

Slide 18.

Future Developments in HD Treatment[1,19]

Slide 19.

Burden of HD on Patients^[1]

Burden of HD on Patients (cont)^[1-3]

Burden of HD on Caregivers and Society^[4]

Treatments for HD^[1,5-6]

Deutetrabenazine: FIRST-HD Trial^[8]

Deutetrabenazine: Safety Profile^[8-9]

Deutetrabenazine: Impact on Patient^[8]

Pridopidine: Control of Voluntary Motor Coordination in HD^[10]

Pridopidine: PRIDE-HD Study^[11]

Potential Impact of Improvements in One Symptom on Other Symptoms^[1,12]

The Role of PCPs in Treating HD^[1,4,12]

The Role of PCPs in Treating HD (cont)^[1,4,12]

Strategies for Developing New HD Therapies^[1,13-16]

Strategies for Developing New HD Therapies (cont)^[1,17-19]

Structural Changes in Brain Prior to Emergence of HD Symptoms^[20-22]

Future Developments in HD Treatment^[1,19]

Concluding Remarks^[23]