% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Ludolph:276161, author = {Ludolph, Albert and Wiesenfarth, Maximilian}, title = {{T}ofersen and other antisense oligonucleotides in {ALS}.}, journal = {Therapeutic advances in neurological disorders}, volume = {18}, issn = {1756-2856}, address = {London [u.a.]}, publisher = {Sage}, reportid = {DZNE-2025-00233}, pages = {17562864251313915}, year = {2025}, abstract = {The advent of antisense oligonucleotide (ASO) therapies in neurodegenerative disorders is associated with enormous hope. Nusinersen treatment was a breakthrough intervention in the recessive disease spinal muscular atrophy, and superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS) seems to be the paradigm disease in dominant degenerative diseases. The results of treatment with the ASO tofersen in SOD1-ALS show that the drug has a convincing beneficial effect on ALS caused by SOD1 mutations, that preclinical studies in rodents predicted the therapeutic effect in the human disease, and that clinical efficacy is associated with a specific sequence of effects of the drug on mechanistic and degenerative biomarkers and, subsequently, functional outcomes such as weight stabilization and ALSFRS-R. Therefore, the enthusiasm seems to be justified; but this should be followed by an attempt to obtain further insights with the goal to improve this therapy. In particular, the following issues are only partially resolved: Which mechanisms are responsible for the clinical effect following the downregulation of SOD1 protein by ASOs? Is long-term downregulation of SOD1 function associated with side effects? Is there an autoimmune response caused by this and other ASO? Is prevention of SOD1-associated ALS possible?}, subtyp = {Review Article}, keywords = {amyotrophic lateral sclerosis (Other) / antisense oligonucleotides (Other) / superoxide dismutase (Other) / tofersen (Other)}, cin = {Clinical Study Center (Ulm)}, ddc = {610}, cid = {I:(DE-2719)5000077}, pnm = {353 - Clinical and Health Care Research (POF4-353)}, pid = {G:(DE-HGF)POF4-353}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:39845577}, pmc = {pmc:PMC11752197}, doi = {10.1177/17562864251313915}, url = {https://pub.dzne.de/record/276161}, }