About SCA-Global

Background

The spinocerebellar ataxias (SCAs) are a group of autosomal dominantly inherited progressive ataxia disorders. More than 40 genetically different SCAs have been defined that mostly follow the nomenclature of SCA followed by a number, except DRPLA.  The most common – SCA1, SCA2, SCA3 and SCA6, which together affect more than half of all families with a history of SCA – are caused by translated CAG repeat expansion mutations that code for an elongated polyglutamine tract within the respective proteins. Other SCAs are caused by non-repeat or by non-translated repeat mutations that affect a variety of different genes.

SCAs have a worldwide distribution, however with variable prevalence rates reported across the world. Despite the large heterogeneity of the various SCAs, people with SCA and their families are facing similar problems. Once started, ataxia takes a relentlessly progressive course leading to disability and often premature death. Ataxia is frequently accompanied by non-ataxia symptoms which considerably impact quality of life. Currently, there is no cure for any SCA. In fact, there are not even symptomatic medical treatments so that management of SCA patients has to rely on physical and speech therapy.

The need for a global initiative

Although a number of large longitudinal cohort studies, such as EUROSCA, RISCA, SPATAX or CRC-SCA provided valuable information on the disease characteristics and natural history of the common polyglutamine SCAs, there remain major knowledge gaps that preclude further progress towards development of effective therapies. Specifically, it is not known whether the longitudinal clinical data that have been obtained in European and North American cohorts are representative for patients from other world regions. Furthermore, the clinical characteristics of the less prevalent SCAs caused by non-repeat mutations remain largely undefined. There is also insufficient knowledge how the diseases impact on everyday life of affected people and their families. A major obstacle on the way towards successful therapeutic trials is the lack of validated biomarkers. The few biomarker studies that have been completed focussed on imaging and included only small patient numbers. Biochemical markers that will be of critical importance in future trials are completely lacking.

Currently, many clinical investigators worldwide are addressing these issues, but due to a lack of a common research infrastructure, clinical research in SCAs often remains fragmented. The JPND-funded ESMI and the NIH-U01 projects are first examples of international collaboration, and may thus serve as a starting point for more intense, global collaboration.

To deal with these multiple challenges, we present the concept of SCA Global, a worldwide initiative for clinical research in SCAs. SCA Global is conceived as a flexible and open research platform, with which we wish to pursue the following goals:

  • To better understand the manifestation, evolution and impact of the various SCAs
  • To develop and validate biomarkers which can be used in future interventional trials
  • To facilitate access to people with SCAs who are willing to participate in clinical trials

Harmonization and standardization

As there are many researchers worldwide who are collecting data and materials of SCAs, but do not collaborate, there is an urgent need to define a common clinical assessment program, a standard imaging protocol and standards for biomaterial sampling and storage. The leading clinical investigators worldwide as well as ataxia lay organizations need to be involved in the standardization process. The goal will be to achieve the highest possible level of conformity and standardization but, on the other hand, to ensure continuity, wherever possible, to allow joint analysis of existing and newly acquired data.

Database

Ideally, the core resource of SCA Global would be a worldwide registry of SCA patients and family members that enables collection of standardized longitudinal clinical data, provides information about available imaging data and biomaterials, and allows to identify patients who are willing to participate in trials.

In the framework of the ESMI project, the SCA Registry has been established, a secure web-based data capture system and database which was developed by 2mt Software GmbH (Ulm, Germany). The SCA Registry contains all data of the EUROSCA and RISCA studies as well as of the ongoing ESMI project. Currently, we are importing data from the CRC-SCA study and the international SPATAX database. The SCA Registry was devised with the intention to make it available to clinical investigators worldwide. It can be accessed through the internet, is easy to use, and encompasses the entire spectrum of SCAs.

Although, the existing SCA Registry will be an extremely valuable resource of SCA Global, use of this database is not a requirement for participation in SCA Global. If investigators are using functional and secure own databases, they will have the opportunity to continue their own database, provided that they follow the agreed common protocols and are willing to share data.

SCA Global around the world

Patient advocacy organisations who have expressed an interest in taking part

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Institutions who have expressed an interest in taking part

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Africa Zambia University of Zambia
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Asia China Second Affiliated Hospital, Zhejiang
University School of Medicine
Asia China Xiangya Hospital, Central South University
Asia India CSIR Institute of Genomics and Integrative Biology
Asia Israel Israeli MJD Association
Asia Japan Tokyo Medical and Dental University
Asia Japan University of Tokyo
Asia Malaysia Hospital Canselor Tuanku Muhriz
Asia Malaysia Universiti Kebangsaan Malaysia Medical
Center
Asia Pakistan Government College University
Asia Taiwan national yang-ming university
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Australia/Oceania Australia Alfred Hospital, Melbourne
Australia/Oceania New Zealand Auckland City Hospital
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Europe Austria Medical University Innsbruck
Europe Czech Republic Centre of Hereditary Ataxias,
Motol University Hospital
Europe France CHU Hautepierre
Europe France University Hospital of Strasbourg
Europe France Sorbonne University
Europe France Pitie Salpetriere Hospital
Europe Germany University Hospital Essen,
University of Duisburg-Essen
Europe Germany German Center for
Neurodegenerative Diseases (DZNE)
Europe Germany University Hospital Heidelberg
Europe Germany University Hospital Schleswig-Holstein (UKSH), Campus Lübeck
Europe Germany University Hospital of Tuebingen
Europe Germany University Hospital
Düsseldorf
Europe Germany Center for Neurology & Hertie Institute for
Clinical Brain Research
Europe Germany RWTH Aachen University
Europe Germany Goethe University
Europe Germany University Hospital Düsseldorf
Europe Germany Dresden University Medical Center
Europe Germany University Hospital Bonn
Europe Hungary University of Pécs
Europe Hungary Semmelweis University
Europe Italy Bambino Gesù Children’s Hospital, IRCCS
Europe Italy Federico II University
Europe Italy IRCCS-Foundation Neurological Institute
Carlo Besta
Europe Italy Città della Salute e della Scienza University
Europe Italy Institute of Translational Pharmacology (IFT)
Europe Italy University of Brescia
Europe Italy Sapienza Rome University
Europe Netherlands Radboud University Medical Centre
Europe Netherlands University Medical Centre Groningen
Europe Poland Institute of Psychiatry and Neurology Warsaw
Europe Portugal IBMC, University of Porto
Europe Portugal Santo António Hospital, Centro Hospitalar de Porto
Europe Portugal University of Coimbra
Europe Portugal University of Minho, Braga
Europe Romania University of Medicine and Pharmacy “Victor Babes”
Europe Spain Hospital Clinic of Barcelona
Europe Spain Vall d’Hebron University Hospital, Barcelona
Europe Spain Basurto University Hospital, Bilbao
Europe Spain University Hospital Marqués de Valdecilla, Santander
Europe Sweden Karolinska University Hospital Huddinge
Europe UK UCL Institute of Neurology, London
Europe UK Essex Centre for Neurological Sciences, Romford
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North America Canada Montreal Neurological Institute, McGill University
North America Canada CHU de Québec – Université Laval
North America Mexico Instituto Nacional de
Neurologia y Neurocirugia Manuel Velasco Suarez
North America USA Albany Medical Center
North America USA Johns Hopskins University
North America USA Triplet Therapeutics, Cambridge
North America USA Feinberg School of Medicine, Northwestern University
North America USA Ohio State University Wexner Medical Center
North America USA University of Florida College of Medicine
North America USA Houston Methodist Hospital
North America USA UCLA Medical Center
North America USA Wesley Neurology Clinic
North America USA National Ataxia Foundation (NAF)
North America USA University of Minnesota
North America USA Columbia University Medical Center
North America USA Columbia University
North America USA Icahn School of Medicine, Mount Sinai
North America USA Creighton University/CHI Health Immanuel
North America USA University of Pennsylvania
North America USA University of Washington
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South America Brasil University of Campinas (UNICAMP)
South America Brasil Universidade Federal do Ceará, Fortaleza
South America Brasil Universidade Federal do Rio Grande do Sul, Porto Alegre
South America Brasil Abahe-Brazilian Association of Hereditary Ataxias (Associacao Brasileira de Ataxias Hereditarias), Sao Paulo
South America Brasil Federal University of Sao Paulo –
Escola Paulista de Medicina

Companies who have expressed an interest in taking part

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SCA Global Steering Committee

On 2 April 2018, the inauguration meeting of the SCA Global initiative was held in Philadelphia. The attendants of the meeting in Philadelphia suggested to form a provisional steering committee that will define and plan the next steps in establishing SCA Global.
Members of the committee include:

  • T. Ashizawa (USA),
  • A. Durr (Paris),
  • L. Jardim (Brasil),
  • T. Klockgether (Germany)
  • Bin-Weng Soong (Taiwan),
  • D. Szmulewicz (Australia)

Tetsuo Ashizawa

Alexandra Durr

Laura Jardim

Thomas Klockgether

Bin-Weng Soong

David Szmulewicz

J. Greenfield (Ataxia UK, Euro-ataxia) and S. Hagen (NAF) will represent patient organisations.

Julie Greenfield

Sue Hagen

H. Graessner (Germany) will act as secretary.

Holm Graessner

Holm Graessner