{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:22:18Z","timestamp":1791404538172,"version":"4.3.3"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Minufiya University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurol Sci"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Tofersen, an antisense oligonucleotide, has recently received FDA and EMA approval for treating amyotrophic lateral sclerosis (ALS) in adults with\n                      <jats:italic>SOD1<\/jats:italic>\n                      gene mutations. This systematic review and meta-analysis synthesized evidence on tofersen\u2019s safety and efficacy in patients with\n                      <jats:italic>SOD1<\/jats:italic>\n                      -related ALS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A comprehensive search of three databases was conducted from inception through October 2024. Eligible studies included clinical trials, observational studies, and case studies. Meta-analyses were conducted using a random-effects model in RevMan.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twelve studies involving 195 patients treated with tofersen met the inclusion criteria, comprising two randomized controlled trials (RCTs), five cohort studies, one case series, and four case reports. Tofersen demonstrated promising effects, notably reducing\n                      <jats:italic>SOD1<\/jats:italic>\n                      levels in cerebrospinal fluid and neurofilament light chain (NfL) in plasma, a biomarker strongly correlated with ALS progression and survival. Meta-analysis of RCTs showed a significantly lower rate of decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores from baseline in the tofersen group compared to placebo (SMD\u2009=\u20090.44, 95% CI [0.05 to 0.83],\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.03) and a significant reduction in the decline of predicted Slow Vital Capacity (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.005). In a pre-post meta-analysis of five studies, a significant decrease in ALS progression rate (ALSFRS-R decline rate) was observed (MD = -0.28, 95% CI [-0.40 to -0.15],\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Reported adverse events were consistent with ALS progression or procedural effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Current evidence suggests that tofersen effectively reduces SOD1 and NfL levels and slow disease progression in\n                      <jats:italic>SOD1<\/jats:italic>\n                      ALS, showing promise as a targeted therapeutic option.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10072-025-07994-2","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T23:38:41Z","timestamp":1737070721000},"page":"1977-1985","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic review and meta-analysis"],"prefix":"10.1007","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3849-0995","authenticated-orcid":false,"given":"Abdullah Ashraf","family":"Hamad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibraheem M.","family":"Alkhawaldeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulqadir J.","family":"Nashwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa","family":"Meshref","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahia","family":"Imam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,17]]},"reference":[{"key":"7994_CR1","doi-asserted-by":"publisher","unstructured":"Huang M, Liu YU, Yao X et al (2024) Variability in SOD1-associated amyotrophic lateral sclerosis: geographic patterns, clinical heterogeneity, molecular alterations, and therapeutic implications. 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