SOD1
Variants in Patients With Amyotrophic Lateral Sclerosis in Central Eastern Europe: From Genetic Testing to
SOD1<
Magui Khazaal, Paula Stretavská, Magdalena Kuźma‐Kozakiewicz, Krzysztof Nieporęcki, Adam Betík, Eva Vlčková, Monika Turčanová Koprušáková, Robert Petrovic, Hakan Cetin, Omar Keritam, Wolfgang Löscher, Christian Eggers, Stephan Iglseder, Radoslav Orenčák, Mária Judit Molnár, Zoltán Grosz, Tamás Szlepák, Blaž Koritnik, Magdalena Anna Koszewicz, Daniel Baumgartner, Lenka Slachtova ABSTRACT
Background
Amyotrophic lateral sclerosis (ALS) is one of the most devastating fatal motor neuron diseases, characterized by progressive degeneration of motor neurons in the brain and spinal cord. A significant advance in ALS therapy was achieved with the recent European Medicines Agency approval of Tofersen, the first antisense oligonucleotide (ASO) specifically targeting SOD1 mRNA, a key genetic determinant of the disease. Yet, despite its clinical relevance, data on SOD1 ‐ALS in Central Eastern Europe remain scarce.
Methods
Here, we present a multicentric study across six countries—Austria, Czechia, Poland, Hungary, Slovakia, and Slovenia—representing approximately 16% of the European Union's population. We report all pathogenic, likely pathogenic, and uncertain SOD1 variants, along with the phenotypic features, including heritability, age, site of onset, and survival. We also assessed the availability of genetic testing, counseling, and access to Tofersen therapy across the region.
Results
Out of 1200 patients with confirmed ALS, we identified 24 distinct pathogenic SOD1 variants in a total of 67 patients (median age at onset 47 [40–55] years), of whom 65.7% had familial ALS (fALS) and 34.3% had sporadic ALS (sALS). We characterized the associated phenotypes and reported that 42 patients are currently receiving Tofersen therapy.
Conclusion
This study provides the first comprehensive overview of SOD1 ‐ALS in Central Eastern Europe. Our findings underscore the importance of genetic testing and counseling, as well as equitable access to targeted therapies such as Tofersen to advance patient‐specific care in this region.