Codrin Lungu1, Laurie Ozelius2, David Standaert2, Mark Hallett2, Beth-Anne Sieber2, Christine Swanson-Fisher2, Brian D Berman2, Nicole Calakos2, Jennifer C Moore2, Joel S Perlmutter2, Sarah E Pirio Richardson2, Rachel Saunders-Pullman2, Laura Scheinfeldt2, Nutan Sharma2, Roy Sillitoe2, Kristina Simonyan2, Philip A Starr2, Anna Taylor2, Jerrold Vitek2. 1. From the Division of Clinical Research (C.L.), National Institute of Neurological Disorders and Stroke, National Institutes of Health; Harvard Medical School (L.O., N.S.), Massachusetts General Hospital, Boston, MA; University of Alabama, Birmingham (D.S.), Birmingham, AL; Medical Neurology Branch (M.H.), NINDS, NIH, Bethesda, MD; Division of Neuroscience (B.-A.S., C.S.-F.), NINDS, NIH, Bethesda, MD; Department of Neurology (B.D.B.), University of Colorado Denver, Aurora, CO; Duke University School of Medicine, Durham, NC; RUCDR/Infinite Biologics (J.C.M.), Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ; Washington University School of Medicine (J.S.P.), St Louis, MO; Department of Neurology (S.E.P.R.), University of New Mexico Health Sciences Center, Albuquerque, NM; Department of Neurology (R.S.-P.), Icahn School of Medicine at Mount Sinai, New York, NY; Coriell Institute for Medical Research (L.S.), Camden, NJ; Department of Neuroscience (R.S.), Baylor College of Medicine, Houston, TX; Harvard Medical School (K.S.), Department of Otolaryngology, Head and Neck Surgery, Massachusetts Eye and Ear Institute, Boston, MA; Department of Neurological Surgery (P.A.S.), University of California San Francisco, San Francisco, CA; Division of Extramural Activities (A.T.), NINDS, NIH, Rockville, MD; and Department of Neurology (J.V.), University of Minnesota, Minneapolis, MN. lunguci@ninds.nih.gov. 2. From the Division of Clinical Research (C.L.), National Institute of Neurological Disorders and Stroke, National Institutes of Health; Harvard Medical School (L.O., N.S.), Massachusetts General Hospital, Boston, MA; University of Alabama, Birmingham (D.S.), Birmingham, AL; Medical Neurology Branch (M.H.), NINDS, NIH, Bethesda, MD; Division of Neuroscience (B.-A.S., C.S.-F.), NINDS, NIH, Bethesda, MD; Department of Neurology (B.D.B.), University of Colorado Denver, Aurora, CO; Duke University School of Medicine, Durham, NC; RUCDR/Infinite Biologics (J.C.M.), Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ; Washington University School of Medicine (J.S.P.), St Louis, MO; Department of Neurology (S.E.P.R.), University of New Mexico Health Sciences Center, Albuquerque, NM; Department of Neurology (R.S.-P.), Icahn School of Medicine at Mount Sinai, New York, NY; Coriell Institute for Medical Research (L.S.), Camden, NJ; Department of Neuroscience (R.S.), Baylor College of Medicine, Houston, TX; Harvard Medical School (K.S.), Department of Otolaryngology, Head and Neck Surgery, Massachusetts Eye and Ear Institute, Boston, MA; Department of Neurological Surgery (P.A.S.), University of California San Francisco, San Francisco, CA; Division of Extramural Activities (A.T.), NINDS, NIH, Rockville, MD; and Department of Neurology (J.V.), University of Minnesota, Minneapolis, MN.
Abstract
OBJECTIVE: Dystonia is a complex movement disorder. Research progress has been difficult, particularly in developing widely effective therapies. This is a review of the current state of knowledge, research gaps, and proposed research priorities. METHODS: The NIH convened leaders in the field for a 2-day workshop. The participants addressed the natural history of the disease, the underlying etiology, the pathophysiology, relevant research technologies, research resources, and therapeutic approaches and attempted to prioritize dystonia research recommendations. RESULTS: The heterogeneity of dystonia poses challenges to research and therapy development. Much can be learned from specific genetic subtypes, and the disorder can be conceptualized along clinical, etiology, and pathophysiology axes. Advances in research technology and pooled resources can accelerate progress. Although etiologically based therapies would be optimal, a focus on circuit abnormalities can provide a convergent common target for symptomatic therapies across dystonia subtypes. The discussions have been integrated into a comprehensive review of all aspects of dystonia. CONCLUSION: Overall research priorities include the generation and integration of high-quality phenotypic and genotypic data, reproducing key features in cellular and animal models, both of basic cellular mechanisms and phenotypes, leveraging new research technologies, and targeting circuit-level dysfunction with therapeutic interventions. Collaboration is necessary both for collection of large data sets and integration of different research methods.
OBJECTIVE:Dystonia is a complex movement disorder. Research progress has been difficult, particularly in developing widely effective therapies. This is a review of the current state of knowledge, research gaps, and proposed research priorities. METHODS: The NIH convened leaders in the field for a 2-day workshop. The participants addressed the natural history of the disease, the underlying etiology, the pathophysiology, relevant research technologies, research resources, and therapeutic approaches and attempted to prioritize dystonia research recommendations. RESULTS: The heterogeneity of dystonia poses challenges to research and therapy development. Much can be learned from specific genetic subtypes, and the disorder can be conceptualized along clinical, etiology, and pathophysiology axes. Advances in research technology and pooled resources can accelerate progress. Although etiologically based therapies would be optimal, a focus on circuit abnormalities can provide a convergent common target for symptomatic therapies across dystonia subtypes. The discussions have been integrated into a comprehensive review of all aspects of dystonia. CONCLUSION: Overall research priorities include the generation and integration of high-quality phenotypic and genotypic data, reproducing key features in cellular and animal models, both of basic cellular mechanisms and phenotypes, leveraging new research technologies, and targeting circuit-level dysfunction with therapeutic interventions. Collaboration is necessary both for collection of large data sets and integration of different research methods.
Authors: Nicole C Swann; Coralie de Hemptinne; Svjetlana Miocinovic; Salman Qasim; Sarah S Wang; Nathan Ziman; Jill L Ostrem; Marta San Luciano; Nicholas B Galifianakis; Philip A Starr Journal: J Neurosci Date: 2016-06-15 Impact factor: 6.167
Authors: L J Ozelius; J W Hewett; C E Page; S B Bressman; P L Kramer; C Shalish; D de Leon; M F Brin; D Raymond; D P Corey; S Fahn; N J Risch; A J Buckler; J F Gusella; X O Breakefield Journal: Nat Genet Date: 1997-09 Impact factor: 38.330
Authors: Aziz M Uluğ; An Vo; Miklos Argyelan; Lauren Tanabe; Wynne K Schiffer; Stephen Dewey; William T Dauer; David Eidelberg Journal: Proc Natl Acad Sci U S A Date: 2011-04-04 Impact factor: 11.205
Authors: Andreas Kupsch; Reiner Benecke; Jörg Müller; Thomas Trottenberg; Gerd-Helge Schneider; Werner Poewe; Wilhelm Eisner; Alexander Wolters; Jan-Uwe Müller; Günther Deuschl; Marcus O Pinsker; Inger Marie Skogseid; Geir Ketil Roeste; Juliane Vollmer-Haase; Angela Brentrup; Martin Krause; Volker Tronnier; Alfons Schnitzler; Jürgen Voges; Guido Nikkhah; Jan Vesper; Markus Naumann; Jens Volkmann Journal: N Engl J Med Date: 2006-11-09 Impact factor: 91.245
Authors: Samuel J Rose; Xin Y Yu; Ann K Heinzer; Porter Harrast; Xueliang Fan; Robert S Raike; Valerie B Thompson; Jean-Francois Pare; David Weinshenker; Yoland Smith; Hyder A Jinnah; Ellen J Hess Journal: Brain Date: 2015-07-27 Impact factor: 13.501
Authors: Cathérine C S Delnooz; Jaco W Pasman; Christian F Beckmann; Bart P C van de Warrenburg Journal: PLoS One Date: 2013-05-01 Impact factor: 3.240
Authors: Zachary F Caffall; Bradley J Wilkes; Ricardo Hernández-Martinez; Joseph E Rittiner; Jennifer T Fox; Kanny K Wan; Miranda K Shipman; Steven A Titus; Ya-Qin Zhang; Samarjit Patnaik; Matthew D Hall; Matthew B Boxer; Min Shen; Zhuyin Li; David E Vaillancourt; Nicole Calakos Journal: Sci Transl Med Date: 2021-08-18 Impact factor: 17.956
Authors: Kristina Simonyan; Stefan K Ehrlich; Richard Andersen; Jonathan Brumberg; Frank Guenther; Mark Hallett; Matthew A Howard; José Del R Millán; Richard B Reilly; Tanja Schultz; Davide Valeriani Journal: Mov Disord Date: 2022-08-10 Impact factor: 9.698
Authors: Anna Sadnicka; Lorenzo Rocchi; Anna Latorre; Elena Antelmi; James Teo; Isabel Pareés; Britt S Hoffland; Kristian Brock; Katja Kornysheva; Mark J Edwards; Kailash P Bhatia; John C Rothwell Journal: Mov Disord Date: 2022-03-21 Impact factor: 9.698
Authors: Meike E van der Heijden; Dominic J Kizek; Ross Perez; Elena K Ruff; Michelle E Ehrlich; Roy V Sillitoe Journal: J Physiol Date: 2021-01-09 Impact factor: 5.182
Authors: Zheng Zhang; Elizabeth Cisneros; Ha Yeon Lee; Jeanne P Vu; Qiyu Chen; Casey N Benadof; Jacob Whitehill; Ryin Rouzbehani; Dominique T Sy; Jeannie S Huang; Terrence J Sejnowski; Joseph Jankovic; Stewart Factor; Christopher G Goetz; Richard L Barbano; Joel S Perlmutter; Hyder A Jinnah; Brian D Berman; Sarah Pirio Richardson; Glenn T Stebbins; Cynthia L Comella; David A Peterson Journal: Ann Clin Transl Neurol Date: 2022-03-25 Impact factor: 5.430