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Symposium 2008, London/Oxford, United Kingdom -

Summary

The Fourth International Neuroacanthocytosis Symposium was based in the historic locale of Worcester College, Oxford, organized by Antonio Velayos-Baeza, PhD. The guest of honour was Prof. Edmund Critchley, who originally described what was initially known as “Levine-Critchley syndrome”. His first patient with this syndrome was observed in1968 during his visit to Kentucky, as described in his biography “A Neurologist´s Tale” (2001). The purpose of this visit, as he nicely describes, was to obtain his BTA qualification (“been to America”), felt to be essential for advancement in British neurology at that time. The patient he described conforms to the typical picture of autosomal recessive chorea-acanthocytosis (ChAc) as now defined by mutations of the VPS13A gene. On return to the UK he recognized the identical picture in a woman from Lancashire, helping to establish the diagnosis in the literature.
 
Participants at the meeting included a core group of researchers who had been present at one or several of the previous symposia, in addition to new attendees from the fields of cell biology and genetics, and outside guest commentators. The focus of the meeting was to address the connections between, and the pathogenesis of, the neuroacanthocytosis (NA) syndromes. These monogenic disorders are characterised by appearance of thorny red blood cells and degeneration of the basal ganglia, and include chorea-acanthocytosis (ChAc), McLeod syndrome (MLS), Huntington’s disease-like 2 (HDL2) and neurodegeneration with brain iron accumulation (NBIA).
 
The first day of the meeting, organised by Susanne Schneider, MD, took place on July 1, 2008 at the Gilliatt Lecture Theatre of The Institute of Neurology, Queen Square, London, chaired by Prof. Kailash Bhatia and Dr. Richard Hardie.  The focus was on reviews of the clinical features of MLS, ChAc, HDL2, NBIA with PANK2 or PLA2G6 mutations, and a disorder now known to be due to mutation of the glucose transporter gene GLUT-1, previously described as familial acanthocytosis with paroxysmal exercise-induced dystonia. Dr. Patricia Limousin led a round table on the application of deep brain stimulation.
 
The second day of the meeting, addressing basic science aspects of the NA syndromes, took place in the Department of Pharmacology, Oxford, chaired by Prof. Anthony P. Monaco, Head of the Neurogenetics Laboratory at the Wellcome Trust Centre for Human Genetics, University of Oxford.  Potential roles for VPS13A were examined in the model organisms yeast and tetrahymena, and include a potential function in phagocytosis, which has recently been proposed to be involved in the pathogenesis of a number of neurodegenerative conditions. Processes involved in red cell membrane shape and physiology were reviewed, with an emphasis on the limited understanding of the proteins which are prominently involved in the cell shape changes of the NA syndromes, including those which make it remarkably deformable under normal circumstances.
 
In order to facilitate international collaboration and to share clinical data and tissue, a patient registry has now been established, open to all healthcare providers, within the European Huntington´s Disease Network: www.euro-hd.net/html/na/submodule.
 
The symposium was endorsed by The Movement Disorder Society and was supported by The Institute of Neurology, London; The Brain Research Trust, London; The National Hospital for Neurology and Neurosurgery, London; The Wellcome Trust Centre for Human Genetics, Oxford; Glaxo Smith Kline; and Livability (John Grooms/The Shaftesbury Society).
The members of the Organizing and Program Committees were: Benedikt Bader, Germany; Kailash Bhatia, UK; Adrian Danek, Germany; Sonia Gandhi, UK; Glenn Irvine, UK; Hans H. Jung, Switzerland; Clotilde Levecque, UK; Anthony P. Monaco, UK; Susanne Schneider, UK; Antonio Velayos-Baeza, UK, and Ruth H. Walker, USA. As with the past symposia since 2002, the support and participation of the Irvine family and The Advocacy for Neuroacanthocytosis Patients (www.naadvocacy.org) was invaluable.
 
The proceedings of the previous meetings have been reported in books (Neuroacanthocytosis Syndromes I and II; Springer, 2004 and 2008) and several reviews had resulted from the Third Symposium at the Movement Disorders Congress in Kyoto (Mov.Disord. 2006, 21:1794; Neurology 2007, 68:92; see also www.geneclinics.org), additional reviews for health care professionals are in preparation. Patients and and families may find support through the Advocacy for Neuroacanthocytosis Patients, a Yahoo group and a face book awareness group initiated by Joanne Tansley. The Advocacy for Neuroacanthocytosis Patients (www.naadvocacy.org) began its work in 2001 and has grown to be a network of patients, their families and friends together with about 300 clinicians and researchers around the world who are concerned with neuroacanthocytosis. The Advocacy carries the cost of the free protein expression test that as long as genetic testing for VPS13A mutations on economical grounds remains unfeasible gives excellent support to a clinical suspicion of ChAc. For the Western blot that in ChAc patients typically shows absence of expression of the VPS13A gene product, chorein, on circulating red cell membranes see www.nefo.med.uni-muenchen.de/~adanek/Chorein_Blot.pdf. The Advocacy also encourages an organ donation program so that in the NA syndromes clues about disease mechanisms can be discovered in deceased patients´ brains. The work of the Advocacy in addition to its website with information in various languages, including Japanese, includes a regular newsletter, financial support for basic and clinical research and contact between patients’ families. 

Programme

Bridging clinical and basic aspects
How do a severe movement disorder phenotype, thorny red blood cells, mutations of single genes and the degeneration of the caudate nucleus relate? This and the state of the art for care of patients with neuroacanthocytosis are the topics to be discussed in meetings at the Institute of Neurology, Queen Square, London and in Oxford.

Programme
Tuesday 01.07.2008 – Queen Square, London

Introduction: movement disorder phenomenology-chaired by Prof. Kailash Bhatia, DM, FRCP, Sobell Institute, Institute of Neurology, University College London
  • Follow–up of cases reported by Dr. R. Hardie in 1991 - Sonia Gandhi, MD, Institute of Neurology, University College London
  • International efforts at case collection (“virtual institute”) - Prof. Dr. Adrian Danek, Neurologische Klinik, Ludwig-Maximilians-Universität, Munich
  • Epilepsy in neuroacanthocytosis - Christian Vollmar, MD, The National Society for Epilepsy, Chalfont St. Peter, Bucks
  • McLeod syndrome: brain and neuromuscular pathology - Hans Jung, MD, Department of Neurology, University Hospital Zurich, Zurich
  • Chorein (VPS13A) expression/neuropathology - Benedikt Bader, MD, Zentrum für Neuropathologie und Prionforschung, Universität München, Munich
  • Caudate nucleus pathology and obsessive-compulsive disorder in ChAc - Mark Walterfang, MD, Neuropsychiatry Unit, Royal Melbourne Hospital, Melbourne

Treatments
  • Drug therapies including botulinum toxin - Susanne Schneider MD, Sobell Institute, Institute of Neurology, University College London
  • Rehabilitation - Qualitative Interviewing - A Patient’s Perspective - Jacqueline McIntosh, Principal Speech and Language Therapist, The Wolfson
  • Neuro rehabilitation Centre, St. George’s Healthcare, Wimbledon
  • Biofeedback in dystonic syndromes – Dr MIWM Horstink, Department of Neurology, Radboud University Medical Centre, Nijmegen

Forum on deep brain stimulation for NA patients led by Patricia Limousin, MD, Institute of Neurology UCL with Professor Philippe Coubes, Gui de Chauliac Hospital, Montpellier, France , Pierre Burbaud,  Centre Hospitalier Pellegrin,  Bordeaux, Jorge Guridi, Pamplona and Lars Timmermann, University of Cologne

Related syndromes
  • Mediators and modulators in Huntington’s Disease – Sarah Tabrizi, MD, Clinical Senior Lecturer, MRC Prion Unit, Institute of Neurology, Queens Square, London
  • Pantothenate kinase-associated neurodegeneration - Susan J. Hayflick, MD, Professor and Interim Chair, Molecular and Medical Genetics, Oregon Health & Science University, Portland, Oregon
  • FAPED – Prof. Alexander Storch, Department of Neurology, Technical University of Dresden, Dresden
  • Huntington’s disease like-2 - Ruth H. Walker, MB, ChB, PhD, Department of Neurology, James J. Peters Veterans Affairs Medical Center, Bronx and Mount Sinai School of Medicine, New York, NY, USA
 
Wednesday 02.07.2008 - Oxford
 
Exploring the clues to neuropathogenesis in neuroacanthocytosis
Chair: Prof. Anthony P. Monaco, Pro-Vice-Chancellor (Planning & Resources) and Head of Neurogenetics Laboratory, Oxford University
 
Genes and proteins
  • Vps13 in yeast - Robert S. Fuller, Ph.D., Professor and Associate Chair of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI
  • The Tetrahymena thermophila Vacuolar Protein Sorting 13A protein (VPS13A) localizes to the membrane of phagosomes - Larry Klobutcher, Associate Dean of the Graduate School, Prof., Dept. of Molecular Microbial and Structural Biology, University of Connecticut Health Center, Farmington, CT
  • Chorein and other human VPS13 proteins - Clotilde Leveque, PhD, Monaco Group, Wellcome Trust Centre for Human Genetics, Oxford
  • Chorein (VPS13A) state and Proteome analysis in ChAc red blood cells – Masayakuki Nakamur, MD PhD, Kagoshima University
  • Identification of genes regulated by genetic variation in VPS13A - Eric K. Moses, PhD Associate Scientist Southwest Foundation for Biomedical Research, San Antonio, TX
  • Recent advances in Kell and XK research - Soohee Lee, PhD, New York Blood Center, New York, NY
  • Pathogenesis of Huntington’s disease-like 2 - Dobrila Rudnicki, PhD, Johns Hopkins Medical Institutions, Department of Psychiatry, Baltimore, MD, USA
 
Reports on current research sponsored by the Advocacy
  • Production of Antibodies against human VPS13 proteins - Antonio Velayos Baeza PhD, Monaco Group, Wellcome Trust Centre for Human Genetics, Oxford
  • Erythrocytes membrane research - Lucia de Franceschi, PhD, Department of Clinical and Experimental Medicine, Section of Internal Medicine, University of Verona
  • Protemic inventory of erythrocytes –Giel Bosman, PhD, Nijmegen Centre for Molecular Life Sciences, Nijmegen
 
Mechanisms of red cell membrane shape changes
  • The molecular basis of red cell membrane disorders - Jean Delaunay, MD, Hopital de Bicetre, Service d’Hematologie, Faculte de Medecine Paris-Sud, Le Kremlin-Bicetre, France
  • Protein interactions in the erythrocyte membrane - Mohandas Narla, DSc, Director, Kimbal Research Institute, New York Blood Center, New York
 
Animal models
  • Molecular understanding of ChAc using ChAc mice – Prof. Akira Sano, Professor and Chairman, Department Kagoshima University
  • Huntington’s disease mice – Anthony J. Hannan, PhD, Head, Neural Plasticity Group, Howard Florey Institute, University of Melbourne, Melbourne
 
Reviews and critique
  • Genes and proteins - Prof John Hardy, Institute of Neurology, UCL, London
  • Structural biology - Rainer Prohaska, PhD, Max F. Perutz Laboratories (MFPL) Medical University of Vienna
Download the PDF version of the symposiums' agenda in the documents section.

The symposium is endorsed by The Movement Disorder Society.

Accomodation available in Worcester College, Oxford University
To propose papers or posters for presentation at the symposium or for more details contact: www.naadvocacy.org or send an email to Glenn Irvine ( ).