Changes in Cerebrospinal Fluid Concentrations of Selenium Species Induced by Tofersen Administration in Subjects with Amyotrophic Lateral Sclerosis Carrying SOD1 Gene Mutations.

Autor: Vinceti M; CREAGEN - Environmental, Genetic, and Nutritional Epidemiology Research Center, Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy. marco.vinceti@unimore.it.; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA. marco.vinceti@unimore.it., Urbano T; CREAGEN - Environmental, Genetic, and Nutritional Epidemiology Research Center, Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy., Filippini T; CREAGEN - Environmental, Genetic, and Nutritional Epidemiology Research Center, Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.; School of Public Health, University of California Berkeley, Berkeley, CA, USA., Bedin R; Center for Neurosciences and Neurotechnology, Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.; Neurology Unit, Modena University Hospital, Modena, Italy., Simonini C; Center for Neurosciences and Neurotechnology, Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.; Neurology Unit, Modena University Hospital, Modena, Italy., Sorarù G; Department of Neurosciences, Neuromuscular Center, University of Padua, Padua, Italy., Trojsi F; Department of Advanced Medical and Surgical Sciences, MRI Research Center, Luigi Vanvitelli Campania University, Naples, Italy.; First Division of Neurology, University Hospital, Luigi Vanvitelli Campania University, Naples, Italy., Michalke B; Research Unit Analytical BioGeoChemistry, Helmholtz Center Munich - German Research Center for Environmental Health, Neuherberg, Germany., Mandrioli J; Center for Neurosciences and Neurotechnology, Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.; Neurology Unit, Modena University Hospital, Modena, Italy.
Jazyk: angličtina
Zdroj: Biological trace element research [Biol Trace Elem Res] 2024 Jul 17. Date of Electronic Publication: 2024 Jul 17.
DOI: 10.1007/s12011-024-04311-4
Abstrakt: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting the brain and spinal cord motor neurons. On 25 April 2023, the drug tofersen, an antisense oligonucleotide, received the US Food and Drug Administration approval for treating ALS in adults carrying mutations of the SOD1 gene. We aimed at assessing whether cerebrospinal fluid concentrations of selenium, an element of both toxicological and nutritional interest possibly involved in disease etiology and progression, are modified by tofersen administration. We determined concentrations of selenium species by anion exchange chromatography hyphenated to inductively coupled plasma-dynamic reaction cell-mass spectrometry and overall selenium by using inductively coupled plasma sector-field mass spectrometry, at baseline and 6 months after active tofersen treatment in ten Italian ALS patients carrying the SOD1 gene mutation. Concentrations of total selenium and many selenium species substantially increased after the intervention, particularly of inorganic (tetravalent and hexavalent) selenium and of the organic species selenomethionine and a compound co-eluting with the selenocystine standard. Overall, these findings suggest that tofersen treatment markedly alters selenium status and probably the redox status within the central nervous system, possibly due to a direct effect on neurons and/or the blood-brain barrier. Further studies are required to investigate the biological and clinical relevance of these findings and how they might relate to the pharmacological effects of the drug and to disease progression.
(© 2024. The Author(s).)
Databáze: MEDLINE
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