Frontiers in Neurology (Jun 2021)

The ARCA Registry: A Collaborative Global Platform for Advancing Trial Readiness in Autosomal Recessive Cerebellar Ataxias

  • Andreas Traschütz,
  • Andreas Traschütz,
  • Selina Reich,
  • Selina Reich,
  • Astrid D. Adarmes,
  • Astrid D. Adarmes,
  • Mathieu Anheim,
  • Mathieu Anheim,
  • Mathieu Anheim,
  • Mahmoud Reza Ashrafi,
  • Jonathan Baets,
  • Jonathan Baets,
  • Jonathan Baets,
  • A. Nazli Basak,
  • Enrico Bertini,
  • Bernard Brais,
  • Cynthia Gagnon,
  • Janina Gburek-Augustat,
  • Hasmet A. Hanagasi,
  • Anna Heinzmann,
  • Rita Horvath,
  • Peter de Jonghe,
  • Peter de Jonghe,
  • Peter de Jonghe,
  • Christoph Kamm,
  • Peter Klivenyi,
  • Thomas Klopstock,
  • Thomas Klopstock,
  • Thomas Klopstock,
  • Martina Minnerop,
  • Martina Minnerop,
  • Martina Minnerop,
  • Alexander Münchau,
  • Mathilde Renaud,
  • Mathilde Renaud,
  • Richard H. Roxburgh,
  • Richard H. Roxburgh,
  • Filippo M. Santorelli,
  • Tommaso Schirinzi,
  • Tommaso Schirinzi,
  • Deborah A. Sival,
  • Dagmar Timmann,
  • Stefan Vielhaber,
  • Stefan Vielhaber,
  • Stefan Vielhaber,
  • Michael Wallner,
  • Bart P. van de Warrenburg,
  • Ginevra Zanni,
  • Stephan Zuchner,
  • Thomas Klockgether,
  • Thomas Klockgether,
  • Rebecca Schüle,
  • Rebecca Schüle,
  • Ludger Schöls,
  • Ludger Schöls,
  • PREPARE Consortium,
  • Matthis Synofzik,
  • Matthis Synofzik

DOI
https://doi.org/10.3389/fneur.2021.677551
Journal volume & issue
Vol. 12

Abstract

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Autosomal recessive cerebellar ataxias (ARCAs) form an ultrarare yet expanding group of neurodegenerative multisystemic diseases affecting the cerebellum and other neurological or non-neurological systems. With the advent of targeted therapies for ARCAs, disease registries have become a precious source of real-world quantitative and qualitative data complementing knowledge from preclinical studies and clinical trials. Here, we review the ARCA Registry, a global collaborative multicenter platform (>15 countries, >30 sites) with the overarching goal to advance trial readiness in ARCAs. It presents a good clinical practice (GCP)- and general data protection regulation (GDPR)-compliant professional-reported registry for multicenter web-based capture of cross-center standardized longitudinal data. Modular electronic case report forms (eCRFs) with core, extended, and optional datasets allow data capture tailored to the participating site's variable interests and resources. The eCRFs cover all key data elements required by regulatory authorities [European Medicines Agency (EMA)] and the European Rare Disease (ERD) platform. They capture genotype, phenotype, and progression and include demographic data, biomarkers, comorbidity, medication, magnetic resonance imaging (MRI), and longitudinal clinician- or patient-reported ratings of ataxia severity, non-ataxia features, disease stage, activities of daily living, and (mental) health status. Moreover, they are aligned to major autosomal-dominant spinocerebellar ataxia (SCA) and sporadic ataxia (SPORTAX) registries in the field, thus allowing for joint and comparative analyses not only across ARCAs but also with SCAs and sporadic ataxias. The registry is at the core of a systematic multi-component ARCA database cluster with a linked biobank and an evolving study database for digital outcome measures. Currently, the registry contains more than 800 patients with almost 1,500 visits representing all ages and disease stages; 65% of patients with established genetic diagnoses capture all the main ARCA genes, and 35% with unsolved diagnoses are targets for advanced next-generation sequencing. The ARCA Registry serves as the backbone of many major European and transatlantic consortia, such as PREPARE, PROSPAX, and the Ataxia Global Initiative, with additional data input from SPORTAX. It has thus become the largest global trial-readiness registry in the ARCA field.

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