MOLECULAR ETIOLOGY OF EARLY ONSET TORSION DYSTONIA

Summary

Principal Investigator: XANDRA OWENS BREAKEFIELD
Abstract: Torsion dystonia is one of the most common and least well understood movement disorder in humans. Affected individuals manifest contracted twisting movements and abnormal postures, which can be crippling. Early onset generalized dystonia (DYT1), the most severe of the hereditary dystonias, is caused by a dominant mutation in the T0R1A gene encoding torsinA. Genetic association studies indicate that this gene may also be involved in the more prevalent adult onset, focal dystonias. This long-standing team will focus on: identifying other genes and mutations involved in dystonia;understanding the function and potential interaction of torsinA with proteins at the cellular level;elucidating the role of torsinA in brain development;and generating conditional DYT1 mouse models which will allow identification of affected brain circuitry and neurotransmitter abnormalities, and provide preclinical models for therapeutic testing. Specifically Dr. Ozelius (Project 1) will focus on identifying genes responsible for penetrance in DYT1 and additional genes underlying non-DYT1 early onset dystonia, as well as variations in these early onset genes that may contribute to later onset dystonias. Dr. Breakefleld (Project 2) will evaluate cellular functions of torsinA and associated proteins including their role in movement of organelles during neuronal migration, processing proteins through the secretory pathway and stress responses in the endoplasmic reticulum. The emphasis of Drs. Bhide and Sharma (Project 3) will be on determining the developmental role of torsinA in neurogenesis and neuronal migration in several brain regions, including motor cortex, striatum and midbrain, and related effects on neuronal numbers, transcription factors and signaling. Drs. Standaert and Li (Project 4) will use conditional torsin-A knockout mice to identify regions of the brain and neurotransmitter systems involved in DYT1 dystonia, and test therapeutic drugs. Dr. Breakefleld will serve as Program Director (Core A). Translational relevance and access to patient information and samples will be provided through the clinical Core B under Dr. Nutan Sharma. These integrated studies capitalize on the extensive and complementary expertise of this group focused on the molecular etiology and pathophysiology of early onset dystonia.
Funding Period: 2000-01-01 - 2014-07-31
more information: NIH RePORT

Top Publications

  1. ncbi Update on treatments for dystonia
    D Cristopher Bragg
    Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
    Curr Neurol Neurosci Rep 14:454. 2014
  2. pmc Enhanced hippocampal long-term potentiation and fear memory in Btbd9 mutant mice
    Mark P DeAndrade
    Interdisciplinary Program in Biomedical Sciences, College of Medicine, University of Florida, Gainesville, Florida, United States of America
    PLoS ONE 7:e35518. 2012
  3. pmc New triggers and non-motor findings in a family with rapid-onset dystonia-parkinsonism
    Richard L Barbano
    Department of Neurology, University of Rochester School of Medicine, Rochester, NY, USA
    Parkinsonism Relat Disord 18:737-41. 2012
  4. pmc Alteration of striatal dopaminergic neurotransmission in a mouse model of DYT11 myoclonus-dystonia
    Lin Zhang
    Department of Neurology, School of Medicine, University of Florida, Gainesville, Florida, United States of America
    PLoS ONE 7:e33669. 2012
  5. pmc Improved motor performance in Dyt1 ΔGAG heterozygous knock-in mice by cerebellar Purkinje-cell specific Dyt1 conditional knocking-out
    Fumiaki Yokoi
    Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610 0236, USA
    Behav Brain Res 230:389-98. 2012
  6. pmc Evidence for altered basal ganglia-brainstem connections in cervical dystonia
    Anne J Blood
    Mood and Motor Control Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America
    PLoS ONE 7:e31654. 2012
  7. ncbi Genetics of dystonia
    Tania Fuchs
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York 10029, USA
    Semin Neurol 31:441-8. 2011
  8. pmc Deep brain stimulation for medically refractory life-threatening status dystonicus in children
    Brian P Walcott
    Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts, USA
    J Neurosurg Pediatr 9:99-102. 2012
  9. pmc Abnormal nuclear envelope in the cerebellar Purkinje cells and impaired motor learning in DYT11 myoclonus-dystonia mouse models
    Fumiaki Yokoi
    Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
    Behav Brain Res 227:12-20. 2012
  10. pmc Dtorsin, the Drosophila ortholog of the early-onset dystonia TOR1A (DYT1), plays a novel role in dopamine metabolism
    Noriko Wakabayashi-Ito
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America
    PLoS ONE 6:e26183. 2011

Research Grants

  1. Synaptic Function: Effects of the Nerve Injury, Repair, and Altered Activity
    Timothy C Cope; Fiscal Year: 2013
  2. Mitochondrial Proteins in Parkinson's Disease
    J Timothy Greenamyre; Fiscal Year: 2013
  3. HEALTHY AGING AND SENILE DEMENTIA
    John Morris; Fiscal Year: 2013
  4. Alzheimer's Disease Research Center
    Douglas R Galasko; Fiscal Year: 2013
  5. Emory Alzheimer's Disease Center
    Allan I Levey; Fiscal Year: 2013
  6. Injury and Recovery in Developing Brain
    Flora M Vaccarino; Fiscal Year: 2013
  7. Spinal Cord Injury, Plasticity and Transplant Mediated Repair
    John D Houle; Fiscal Year: 2013
  8. UNMC EPPLEY CANCER CENTER SUPPORT GRANT
    Kenneth H Cowan; Fiscal Year: 2013

Detail Information

Publications54

  1. ncbi Update on treatments for dystonia
    D Cristopher Bragg
    Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
    Curr Neurol Neurosci Rep 14:454. 2014
    ..We will also review the current treatment approaches and suggest ways in which these therapies can be applied to individuals with dystonia. ..
  2. pmc Enhanced hippocampal long-term potentiation and fear memory in Btbd9 mutant mice
    Mark P DeAndrade
    Interdisciplinary Program in Biomedical Sciences, College of Medicine, University of Florida, Gainesville, Florida, United States of America
    PLoS ONE 7:e35518. 2012
    ..Further analyses of the mutant mice will help shine light on the function of BTBD9 and its role in RLS...
  3. pmc New triggers and non-motor findings in a family with rapid-onset dystonia-parkinsonism
    Richard L Barbano
    Department of Neurology, University of Rochester School of Medicine, Rochester, NY, USA
    Parkinsonism Relat Disord 18:737-41. 2012
    ..Rapid-onset dystonia-parkinsonism (RDP) was not suspected until 3 affected children (2 male, 1 female) with presentations consistent with the disorder were recognized...
  4. pmc Alteration of striatal dopaminergic neurotransmission in a mouse model of DYT11 myoclonus-dystonia
    Lin Zhang
    Department of Neurology, School of Medicine, University of Florida, Gainesville, Florida, United States of America
    PLoS ONE 7:e33669. 2012
    ..Neuroimaging studies of DYT11 M-D patients show reduced dopamine D2 receptor (D2R) availability, although the possibility of increased endogenous dopamine, and consequently, competitive D2R occupancy cannot be ruled out...
  5. pmc Improved motor performance in Dyt1 ΔGAG heterozygous knock-in mice by cerebellar Purkinje-cell specific Dyt1 conditional knocking-out
    Fumiaki Yokoi
    Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610 0236, USA
    Behav Brain Res 230:389-98. 2012
    ..The results suggest that molecular lesions of torsinA in Purkinje cells by gene therapy or intervening in the signaling pathway downstream of the cerebellar Purkinje cells may rescue motor symptoms in dystonia 1...
  6. pmc Evidence for altered basal ganglia-brainstem connections in cervical dystonia
    Anne J Blood
    Mood and Motor Control Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America
    PLoS ONE 7:e31654. 2012
    ..While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia...
  7. ncbi Genetics of dystonia
    Tania Fuchs
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York 10029, USA
    Semin Neurol 31:441-8. 2011
    ..Currently, 19 loci including 10 genes have been identified for inherited dystonias. In this review, the phenotypes associated with these loci and the responsible genes will be discussed...
  8. pmc Deep brain stimulation for medically refractory life-threatening status dystonicus in children
    Brian P Walcott
    Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts, USA
    J Neurosurg Pediatr 9:99-102. 2012
    ..Bilateral globus pallidus internus stimulation appears to be effective in the urgent treatment of medically refractory and life-threatening movement disorders...
  9. pmc Abnormal nuclear envelope in the cerebellar Purkinje cells and impaired motor learning in DYT11 myoclonus-dystonia mouse models
    Fumiaki Yokoi
    Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
    Behav Brain Res 227:12-20. 2012
    ....
  10. pmc Dtorsin, the Drosophila ortholog of the early-onset dystonia TOR1A (DYT1), plays a novel role in dopamine metabolism
    Noriko Wakabayashi-Ito
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America
    PLoS ONE 6:e26183. 2011
    ..This dtorsin mutant line will be valuable for understanding this relationship and potentially other novel torsin functions that could play a role in human dystonia...
  11. pmc Motor deficits and decreased striatal dopamine receptor 2 binding activity in the striatum-specific Dyt1 conditional knockout mice
    Fumiaki Yokoi
    Department of Neurology, College of Medicine, University of Florida, Gainesville, Florida, United States of America
    PLoS ONE 6:e24539. 2011
    ..The results suggest that the loss of striatal torsinA alone is sufficient to produce motor deficits, and that this effect may be mediated, at least in part, through changes in D2R function in the basal ganglia circuit...
  12. pmc Developmental profile of the aberrant dopamine D2 receptor response in striatal cholinergic interneurons in DYT1 dystonia
    Giuseppe Sciamanna
    Department of Neuroscience, University Tor Vergata, Rome, Italy
    PLoS ONE 6:e24261. 2011
    ..DYT1 dystonia, a severe form of genetically determined human dystonia, exhibits reduced penetrance among carriers and begins usually during adolescence. The reasons for such age dependence and variability remain unclear...
  13. pmc Cholinergic dysregulation produced by selective inactivation of the dystonia-associated protein torsinA
    Giuseppe Sciamanna
    Clinica Neurologica, Dipartimento di Neuroscienze, Università di Roma Tor Vergata and Fondazione Santa Lucia, I R C C S, Rome, Italy
    Neurobiol Dis 47:416-27. 2012
    ..These results demonstrate a cell-autonomous effect of Dyt1 deletion on striatal cholinergic function. Therapies directed at modifying the function of cholinergic neurons may prove useful in the treatment of the human disorder...
  14. pmc Motor restlessness, sleep disturbances, thermal sensory alterations and elevated serum iron levels in Btbd9 mutant mice
    Mark P DeAndrade
    Interdisciplinary Program in Biomedical Sciences and Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
    Hum Mol Genet 21:3984-92. 2012
    ..Finally, our data argue for the utility of Btbd9 mutant mice to discover and screen novel therapeutics for RLS...
  15. ncbi Clinical neurogenetics: dystonia from phenotype to genotype
    Jeffrey L Waugh
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MA, USA Department of Neurology, Boston Children s Hospital, MA, USA Electronic address
    Neurol Clin 31:969-86. 2013
    ....
  16. pmc Dopa-responsive dystonia: functional analysis of single nucleotide substitutions within the 5' untranslated GCH1 region
    Ioanna A Armata
    Department of Neurogenetics, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 8:e76975. 2013
    ..The biologic significance of these 5'UTR GCH1 sequence substitutions has not been analyzed...
  17. ncbi Pallidal deep brain stimulation for dystonia: a case series
    Melita T Petrossian
    Department of Neurology, Brigham and Women s Hospital and
    J Neurosurg Pediatr 12:582-7. 2013
    ..However, there are limited data on long-term outcome and treatment complications. The authors report on the short- and long-term effects of pallidal DBS in a cohort of patients with early-onset dystonia...
  18. pmc Pre-synaptic release deficits in a DYT1 dystonia mouse model
    Fumiaki Yokoi
    Department of Neurology, College of Medicine, University of Florida, Gainesville, Florida, USA
    PLoS ONE 8:e72491. 2013
    ....
  19. pmc Engineering animal models of dystonia
    Janneth Oleas
    Department of Neurology, College of Medicine, University of Florida, Gainesville, Florida 32610, USA
    Mov Disord 28:990-1000. 2013
    ..These results indicate that genetic animal models are powerful tools to elucidate the pathophysiology and to further develop new therapeutics for dystonia...
  20. pmc Mutations in GNAL cause primary torsion dystonia
    Tania Fuchs
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA
    Nat Genet 45:88-92. 2013
    ..Val137Met in the other. Screening of GNAL in 39 families with PTD identified 6 additional new mutations in this gene. Impaired function of several of the mutants was shown by bioluminescence resonance energy transfer (BRET) assays...
  21. pmc Evaluation of TorsinA as a target for Parkinson disease therapy in mouse models
    Xinru Li
    Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America
    PLoS ONE 7:e50063. 2012
    ..Nevertheless, these data do seem to support the view that torsinA is unlikely to be successfully translated as a target of therapy for human PD...
  22. pmc Neurogenesis and neuronal migration in the forebrain of the TorsinA knockout mouse embryo
    Deirdre M McCarthy
    Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32303, USA
    Dev Neurosci 34:366-78. 2012
    ..These subtle developmental changes are consistent with a lack of significant changes in neuronal numbers, neuronal positioning or size of brain regions in DYT1 dystonia patients...
  23. pmc Cholinergic dysfunction alters synaptic integration between thalamostriatal and corticostriatal inputs in DYT1 dystonia
    Giuseppe Sciamanna
    Department of Neuroscience, University Tor Vergata Laboratory of Neurophysiology and Synaptic Plasticity, Fondazione Santa Lucia Istituto di Ricovero e Cura a Carattere Scientifico, 00143 Rome, Italy
    J Neurosci 32:11991-2004. 2012
    ....
  24. pmc Psychiatric disorders in rapid-onset dystonia-parkinsonism
    Allison Brashear
    Department of Neurology, Wake Forest School of Medicine, Wake Forest Baptist Health, Winston Salem, NC, USA
    Neurology 79:1168-73. 2012
    ..This study examines psychiatric morbidity for 23 patients with RDP in 10 families with family member control subjects and in 3 unrelated patients with RDP, totaling 56 individuals...
  25. pmc Genetically engineered microvesicles carrying suicide mRNA/protein inhibit schwannoma tumor growth
    Arda Mizrak
    Department of Neurology and Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA
    Mol Ther 21:101-8. 2013
    ..Taken together, these studies suggest that MVs can serve as novel cell-derived "liposomes" to effectively deliver therapeutic mRNA/proteins to treatment of diseases...
  26. pmc Dimerization of the DYT6 dystonia protein, THAP1, requires residues within the coiled-coil domain
    Cem Sengel
    Neuroscience Center, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Neurochem 118:1087-100. 2011
    ..These observations offer additional insight into the role of the coiled-coil domain in THAP1, which may facilitate future analyses of DYT6 mutations in this region...
  27. pmc TorsinA participates in endoplasmic reticulum-associated degradation
    Flavia C Nery
    1 Neuroscience Center, Department of Neurology, and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02114, USA 2
    Nat Commun 2:393. 2011
    ..Therefore, compromised ERAD function in the cells of DYT1 patients may increase sensitivity to endoplasmic reticulum stress with consequent alterations in neuronal function contributing to the disease state...
  28. pmc Impairment of bidirectional synaptic plasticity in the striatum of a mouse model of DYT1 dystonia: role of endogenous acetylcholine
    Giuseppina Martella
    Department of Neuroscience, University Tor Vergata, 00133 Rome, Italy
    Brain 132:2336-49. 2009
    ..More importantly, our results indicate that an unbalanced cholinergic transmission plays a pivotal role in these alterations, providing a clue to understand the ability of anticholinergic agents to restore motor deficits in dystonia...
  29. pmc Impaired striatal D2 receptor function leads to enhanced GABA transmission in a mouse model of DYT1 dystonia
    Giuseppe Sciamanna
    Department of Neuroscience, University Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
    Neurobiol Dis 34:133-45. 2009
    ..Our findings demonstrate a disinhibition of striatal GABAergic synaptic activity, that can be at least partially attributed to a D2 DA receptor dysfunction...
  30. ncbi The pathophysiological basis of dystonias
    Xandra O Breakefield
    Department of Neurology and Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Nat Rev Neurosci 9:222-34. 2008
    ....
  31. pmc siRNA knock-down of mutant torsinA restores processing through secretory pathway in DYT1 dystonia cells
    Jeffrey W Hewett
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Hum Mol Genet 17:1436-45. 2008
    ..The ability of allele-specific siRNA for torsinADeltaE to normalize secretory function in DYT1 patient cells supports its potential role as a therapeutic agent in early onset torsion dystonia...
  32. ncbi Phenotypic spectrum and sex effects in eleven myoclonus-dystonia families with epsilon-sarcoglycan mutations
    Deborah Raymond
    The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, New York 10003, USA
    Mov Disord 23:588-92. 2008
    ..0097). We found no association between mutation type and phenotype...
  33. ncbi Dopamine release is impaired in a mouse model of DYT1 dystonia
    Aygul Balcioglu
    MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
    J Neurochem 102:783-8. 2007
    ..The defect in DA release as observed may contribute to the abnormalities in motor learning as previously documented in this transgenic mouse model, and may contribute to the clinical symptoms of the human disorder...
  34. pmc Intragenic Cis and Trans modification of genetic susceptibility in DYT1 torsion dystonia
    Neil J Risch
    Institute for Human Genetics, University of California at San Francisco, San Francisco, CA 94143, USA
    Am J Hum Genet 80:1188-93. 2007
    ..Our findings establish, for the first time, a clinically relevant gene modifier of DYT1...
  35. pmc Mutant torsinA interferes with protein processing through the secretory pathway in DYT1 dystonia cells
    Jeffrey W Hewett
    Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 104:7271-6. 2007
    ..These studies demonstrate the exquisite sensitivity of this reporter system for quantitation of processing through the secretory pathway and support a role for torsinA as an ER chaperone protein...
  36. ncbi Altered responses to dopaminergic D2 receptor activation and N-type calcium currents in striatal cholinergic interneurons in a mouse model of DYT1 dystonia
    A Pisani
    Clinica Neurologica, Dipartimento di Neuroscienze, Universita Tor Vergata, Rome, Italy, and Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA
    Neurobiol Dis 24:318-25. 2006
    ..Our data support the existence of an imbalance between striatal dopaminergic and cholinergic signaling in DYT1 dystonia...
  37. ncbi Effects of genetic variations in the dystonia protein torsinA: identification of polymorphism at residue 216 as protein modifier
    Norman Kock
    Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA
    Hum Mol Genet 15:1355-64. 2006
    ..They also suggest possible connections between the allelic polymorphism at residue 216 and the penetrance of DYT1 dystonia, as well as a possible role for this polymorphism in related disease states...
  38. ncbi Dystonia-causing mutant torsinA inhibits cell adhesion and neurite extension through interference with cytoskeletal dynamics
    Jeffrey W Hewett
    Molecular Neurogenetics Unit, Departments of Neurology and Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA 02114, USA
    Neurobiol Dis 22:98-111. 2006
    ....
  39. pmc Chemical enhancement of torsinA function in cell and animal models of torsion dystonia
    Songsong Cao
    Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA
    Dis Model Mech 3:386-96. 2010
    ....
  40. pmc Dopamine D2 receptor dysfunction is rescued by adenosine A2A receptor antagonism in a model of DYT1 dystonia
    Francesco Napolitano
    CEINGE Biotecnologie Avanzate, Naples, Italy
    Neurobiol Dis 38:434-45. 2010
    ....
  41. pmc The early-onset torsion dystonia-associated protein, torsinA, is a homeostatic regulator of endoplasmic reticulum stress response
    Pan Chen
    Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA
    Hum Mol Genet 19:3502-15. 2010
    ....
  42. ncbi Milestones in dystonia
    Laurie J Ozelius
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA
    Mov Disord 26:1106-26. 2011
    ..The challenge ahead includes continued advancement into understanding dystonia's many underlying causes and associated pathology and using this knowledge to advance treatment including preventing genetic disease expression...
  43. pmc Altered dendritic morphology of Purkinje cells in Dyt1 ΔGAG knock-in and purkinje cell-specific Dyt1 conditional knockout mice
    Lin Zhang
    Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
    PLoS ONE 6:e18357. 2011
    ..Although structural and functional alterations in the cerebellum have been reported in DYT1 dystonia, neuronal morphology has not been examined in vivo...
  44. pmc Update on the pathology of dystonia
    David G Standaert
    Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, AL 35294, USA
    Neurobiol Dis 42:148-51. 2011
    ..Overall the number of well-documented pathological cases available for study is few, and there is an urgent need for additional postmortem studies. This article is part of a Special Issue entitled "Advances in dystonia"...
  45. pmc Genetic and clinical features of primary torsion dystonia
    Laurie J Ozelius
    Departments of Genetics and Genomic Sciences and Neurology, Mount Sinai School of Medicine, One Gustave L Levy Pl, Box 1498 New York, NY 10029, USA
    Neurobiol Dis 42:127-35. 2011
    ..In this review we will describe the phenotypes associated with these loci and discuss the responsible gene. This article is part of a Special Issue entitled "Advances in dystonia"...
  46. pmc Molecular pathways in dystonia
    D Cristopher Bragg
    Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA
    Neurobiol Dis 42:136-47. 2011
    ..This review focuses on these molecular pathways, highlighting potential common themes among these dystonias which may serve as areas for future research. This article is part of a Special Issue entitled "Advances in dystonia"...
  47. pmc Healing genes in the nervous system
    Xandra O Breakefield
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Neuron 68:178-81. 2010
    ....
  48. pmc Direct interaction between causative genes of DYT1 and DYT6 primary dystonia
    Sophie Gavarini
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA
    Ann Neurol 68:549-53. 2010
    ..Our findings provide the first evidence that causative genes for primary dystonia intersect in a common pathway and raise the possibility of developing novel therapies targeting this pathway...
  49. pmc Characterization of Atp1a3 mutant mice as a model of rapid-onset dystonia with parkinsonism
    Mark P DeAndrade
    Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Behav Brain Res 216:659-65. 2011
    ..These results suggest that the Atp1a3 mutant mouse models several characteristics of RDP and further analysis of this mouse model will provide great insight into pathogenesis of RDP...
  50. pmc Genetic evidence for an association of the TOR1A locus with segmental/focal dystonia
    Nutan Sharma
    Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
    Mov Disord 25:2183-7. 2010
    ..In contrast, we did not find an association of either allele at the D216H SNP (rs1801968) with focal or segmental dystonia in the same cohort...
  51. pmc Earlier onset of motor deficits in mice with double mutations in Dyt1 and Sgce
    Fumiaki Yokoi
    Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL 35294 USA
    J Biochem 148:459-66. 2010
    ..Examining additional mutations in other dystonia genes may be beneficial to predict the onset in DYT1 mutation carriers...
  52. ncbi RNAi blocks DYT1 mutant torsinA inclusions in neurons
    Norman Kock
    Departments of Neurology and Radiology, Massachusetts General Hospital, and Neuroscience Program, Harvard Medical School, Boston, USA
    Neurosci Lett 395:201-5. 2006
    ..Vector-delivered siRNAs have the potential to decrease the adverse effects of this mutant protein in neurons without affecting wild-type protein...

Research Grants30

  1. Synaptic Function: Effects of the Nerve Injury, Repair, and Altered Activity
    Timothy C Cope; Fiscal Year: 2013
    ..The Resume and Summary of Discussion above summarizes the final outcome of the group discussion. OVERALL PROGRAM EVALUATION ..
  2. Mitochondrial Proteins in Parkinson's Disease
    J Timothy Greenamyre; Fiscal Year: 2013
    ....
  3. HEALTHY AGING AND SENILE DEMENTIA
    John Morris; Fiscal Year: 2013
    ..Together, these projects and their supporting cores will focus on preclinical DAT in comparison with healthy brain aging and address the issue of detecting preclinical disease. ..
  4. Alzheimer's Disease Research Center
    Douglas R Galasko; Fiscal Year: 2013
    ..It will provide an environment and core resources to enhance research, foster professional and community training, and coordinate interdisciplinary research. ..
  5. Emory Alzheimer's Disease Center
    Allan I Levey; Fiscal Year: 2013
    ..abstract_text> ..
  6. Injury and Recovery in Developing Brain
    Flora M Vaccarino; Fiscal Year: 2013
    ..The long-term goal of these studies is to identify new means of therapeutic intervention to decrease the developmental disability and neurobehavioral sequelae of preterm birth. ..
  7. Spinal Cord Injury, Plasticity and Transplant Mediated Repair
    John D Houle; Fiscal Year: 2013
    ..This Program Project has direct relevance to the design and implementation of future treatment programs for acute and delayed intervention after SCI. ..
  8. UNMC EPPLEY CANCER CENTER SUPPORT GRANT
    Kenneth H Cowan; Fiscal Year: 2013
    ....