The First Scientific Workshop of Hallervorden-Spatz Syndrome
Grant Number: NS40452-01
May 19 - 20, 2000
National Institute of Neurological Disorders & Stroke, Bethesda, Maryland
Principal Investigator: Susan J. Hayflick, MD
Organization Conducting Meeting: Hallervorden-Spatz Syndrome Association and Oregon Health Sciences University
This meeting marked the first time that investigators have met to discuss the current state of knowledge about HSS and to define resources needed and recommend directions for future research. Since few scientists currently study HSS, the meeting also had the goal of stimulating interest in the disorder among young investigators whose current work relates to HSS.
From the presentations a number of key issues became clear. HSS is a highly variable condition with evidence for locus heterogeneity. Existing clinical criteria do not delineate a genetically homogeneous disease. Data from the International Registry of Patients with Hallervorden-Spatz Syndrome and Related Disorders indicate that disease can be best delineated based on clinical, radiographic and genetic features. Participants recommended studies to determine whether a phenotype exists outside of the central nervous system. Reports of ceroid laden bone marrow macrophages raise this question; however, this feature is not found in all patients with classical HSS. Complete delineation of the HSS phenotype as well as functional MRI studies of brains of people affected by HSS may contribute understanding to the pathophysiology of this disease.
Among the first recommendations from this meeting is the need to identify and investigate the major genes that cause HSS and related disorders. Once the major gene is identified, the development of an animal model with HSS will enable scientists from many disciplines and throughout the world to study HSS. Broad research questions that would benefit the study of HSS include delineating the role of iron in the central nervous system and, as a corollary, the reason for its differential distribution in brain. The participants recommended targeted funding in order to attract more scientists into HSS research
Workshop participants agreed that the most important resource needed to advance research on HSS is brain tissue from affected individuals. Most published studies on HSS brain predate modern techniques to prevent leaching of iron from tissue and maintain iron in its biological oxidation state. Furthermore, clinical descriptions have been limited, thus confounding an accurate diagnosis. Studies are needed to accurately document the pathologic changes that occur in classical HSS and related disorders. Tissue must be handled by experienced pathologists who can plan ahead to prepare the samples to maximize their potential for use in investigation. Unfortunately, most brain samples that have been collected in the past from patients with HSS who have died are not able to be used for the needed studies. Participants recommended working with existing brain banks to obtain and process tissue. However, concern was raised about the mechanisms currently in place to ascertain and handle HSS brain tissue for iron studies and other uncommon studies. The recommendation was made to ask the brain banks to delineate techniques for handling brain that would enable these types of studies. These methods must be established and widely disseminated to all participating sites. Tissue other than brain is also needed for research.
Meeting participants voiced an interest in exploring new drug therapies, including free radical scavengers and chelators that target the CNS. At the same time, the group felt that surgical therapies had been discouraging in most patients with HSS. Further studies are needed to confirm this observation.
The NIH sponsored workshop was held in conjunction with the first Hallervorden-Spatz Syndrome Association family meeting in Bethesda. The coordinated organization of these meetings enabled a valuable information exchange between scientists and families.
Proceedings of the Scientific Workshop are currently in review through the journal Pediatric Neurology. Upon publication, they will be widely disseminated.
Specific Recommendations:
Greg Anderson, PhD
The Queensland Institute of Medical Research
Pierre Castelnau, MD, PhD
Hopital Robert Debre
Chuang C. Chiueh, PhD
NIMH, Laboratory of Clinical Sciences
James Conner, PhD
Pennsylvania State Univ. College of Medicine
Adriana Donovan, PhD
Children's Hospital
Howard Hughes Medical Institute
Elizabeth Dooling, MD
Massachusetts General Hospital
Debbie Forstall
Secretary, Hallervorden-Spatz Syndrome Association
Jane Gitschier, PhD
Howard Hughes Medical Institute
University of California, San Francisco
Mark Hallett, MD
National Institutes of Health
Z. Leah Harris, MD
Washington University School of Medicine
Donald Harter, MD
Howard Hughes Medical Institute
Susan J. Hayflick, MD
Oregon Health Sciences University
Monique Johnson, PhD
Oregon Health Sciences University
David Koeller, MD
University of Colorado Health Sciences Center
Arnulf Koeppen, MD
VA Medical Center, Albany
Steve LeVine, PhD
University of Kansas Medical Center
Barbara Levinson
University of California, San Francisco
Kris McGourthy
Hallervorden-Spatz Syndrome Association
Michael McGourthy
Hallervorden-Spatz Syndrome Association
Jonathan Mink, MD
Washington University School of Medicine
Torben Moos, MD
The Panum Institute, University of Copenhagen
Nardo Nardocci, MD
Instituto Neurologico "C.Besta"
Massimo Pandolfo, MD
Centre Hospitalier de l"Universite de Montreal
Zhong Ming Qian, PhD
The Hong Kong Polytechnic University
Tracy Rouault, MD
Section on Human Iron Metabolism NICHD
Michael Shevell, MD, CM, FRCP
Montreal Children's Hospital
Leslie Shinobu, MD, PhD
Massachusetts General Hospital
Giovanna Spinella, MD
NINDS
Kenneth Swaiman, MD
University of Minnesota Medical School
Christopher Vulpe, MD, PhD
University of California, Berkeley
Patricia Wood
President, Hallervorden-Spatz Syndrome Association
Shawn Westaway, PhD
Oregon Health Sciences University
Rob Wilson, MD, PhD
University of Pennsylvania Medical Center
Ke-Wei Zhao, PhD
UCLA School of Medicine
Bing Zhou, PhD
University of California, San Francisco
Last updated February 09, 2005