SOD1 gene screening in ALS - frequency of mutations, patients' attitudes to genetic information and transition to tofersen treatment in a multi-center program

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Thomas Meyer - , Berlin Institute of Health at Charité, Ambulanzpartner Soziotechnologie APST GmbH, Berlin, Germany. (Author)
  • Peggy Schumann - , Ambulanzpartner Soziotechnologie APST GmbH, Berlin, Germany. (Author)
  • Torsten Grehl - , Alfried Krupp Krankenhaus (Author)
  • Ute Weyen - , BG University Hospital Bergmannsheil Bochum (Author)
  • Susanne Petri - , Hannover Medical School (MHH) (Author)
  • Annekathrin Rödiger - , Jena University Hospital (Author)
  • Robert Steinbach - , Jena University Hospital (Author)
  • Julian Grosskreutz - , Universitätsklinikum Schleswig-Holstein - Campus Lübeck (Author)
  • Sarah Bernsen - , German Center for Neurodegenerative Diseases (DZNE) - Partner Site Bonn (Author)
  • Patrick Weydt - , German Center for Neurodegenerative Diseases (DZNE) - Partner Site Bonn (Author)
  • Joachim Wolf - , Diakonissenkrankenhaus Mannheim (Author)
  • René Günther - , Department of Neurology, German Center for Neurodegenerative Diseases, Dresden site (Partner: DZNE of the Helmholtz Association), University Hospital Carl Gustav Carus Dresden (Author)
  • Maximilian Vidovic - , Department of Neurology, University Hospital Carl Gustav Carus Dresden (Author)
  • Petra Baum - , University Hospital Leipzig (Author)
  • Moritz Metelmann - , University Hospital Leipzig (Author)
  • Jochen H Weishaupt - , Universitätsmedizin Mannheim (Author)
  • Berthold Streubel - , Medical University of Wien, Institute for Pathology, Wien, Austria. (Author)
  • David C Kasper - , ARCHIMED Life Science GmbH, Wien, Austria. (Author)
  • Yasemin Koc - , Berlin Institute of Health at Charité (Author)
  • Dagmar Kettemann - , Berlin Institute of Health at Charité (Author)
  • Jenny Norden - , Berlin Institute of Health at Charité (Author)
  • Philipp Schmitt - , Berlin Institute of Health at Charité (Author)
  • Bertram Walter - , Berlin Institute of Health at Charité (Author)
  • Christoph Münch - , Ambulanzpartner Soziotechnologie APST GmbH, Berlin, Germany. (Author)
  • Susanne Spittel - , Ambulanzpartner Soziotechnologie APST GmbH, Berlin, Germany. (Author)
  • André Maier - , Berlin Institute of Health at Charité (Author)
  • Péter Körtvélyessy - , Berlin Institute of Health at Charité (Author)

Abstract

Objective: To report the frequency of pathogenic SOD1 gene variants in a screening program in amyotrophic lateral sclerosis (ALS), and the clinical practice of transition to an expanded access program (EAP) of tofersen treatment. Methods: From October 2021 to February 2024, at 11 ALS centers in Germany genetic testing for SOD1, FUS, TARDBP, and C9orf72 was performed. Patients were offered to opt for notification either about all genetic variants or SOD1 variants relevant for tofersen therapy. The transition to the EAP with tofersen was assessed. Results: 1935 patients were screened (94.7% sporadic ALS). 48.8% (n = 928) opted for notification of treatment-relevant information. Genetic variants were found as follows: SOD1 (likely) pathogenic variants (class 4/5) 1.8% (n = 34), variants of unknown significance (class 3) 0.8% (n = 16), FUS (class 4/5) 0.9% (n = 17), TARDBP (class 4/5) 1.3% (n = 25), C9orf72 hexanucleotide repeat expansion 7.0% (n = 135). In SOD1-ALS (encompassing class 3-5 variants, n = 50), 68.0% (n = 34) reported a negative family history. 74.0% (n = 37) of SOD1-ALS patients - which represent 1.9% of all participants of the screening program - were transitioned to tofersen. Median duration from start of genetic testing to treatment was 94 days (57 to 295 days). Eight patients declined treatment whereas five individuals died before initiation of therapy. Conclusion: The finding of SOD1 variants in patients with a negative family history underscores the need for a broad genetic screening in ALS. In SOD1-ALS, the treatment option with tofersen was mostly utilized. The wide range in the transition time to tofersen calls for a SOD1-ALS management program.

Details

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalAmyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Publication statusE-pub ahead of print - 13 Sept 2024
Peer-reviewedYes

External IDs

Scopus 85204009857

Keywords